Pembrolizumab significantly extended disease-free survival among patients with stage IB to IIIA non–small-cell lung cancer (NSCLC) in the adjuvant setting following surgical resection, according to an interim analysis of the phase 3 KEYNOTE-091 trial (also known as EORTC-1416-LCG/ETOP-8-15 – PEARLS [NCT02504372]).

 Notably, the observed significant improvement in comparison with placebo, which met the trial’s primary end point, was seen across participants regardless of PD-L1 expression.

Interim findings demonstrated that patients whose tumors did express PD-L1 with a tumor proportion score (TPS) of 50% or higher experienced improved DFS following pembrolizumab treatment, however, there was not enough statistically significant linked to this dual primary end point in accordance with the prespecified statistical plan. Researchers will continue to assess DFS in patients whose tumors harbor high levels of PD-L1 and assess overall survival (OS) as a key secondary end point.

Pembrolizumab is an anti–programmed death receptor-1 (PD-1) therapy which functions by blocking the interaction between PD-1 and its ligands PD-L1 and PD-L2, thus activating T lymphocytes and increasing the body’s immune system to help detect and fight tumor cells. KEYNOTE-091 represents the first positive trial to assess this agent in the adjuvant setting of NSCLC, which is known to be the most common form of lung cancer, and which accounts for 85% of lung cancer cases.


“Surgery is widely considered the first and most important intervention for most patients with early-stage non-small cell lung cancer; however, an estimated 43% of those who undergo surgery will see their disease return,” co-principal investigator Mary O’Brien, MD, FRCP, The Royal Marsden, NHS Foundation Trust, and professor at Imperial College, London, UK, said in a news release. “Data from KEYNOTE-091 suggest adjuvant [pembrolizumab] reduced the risk of disease recurrence or death after surgery in the overall population of patients with stage IB to IIIA non–small cell lung cancer.”

KEYNOTE-091 enrolled 1177 patients who were randomized 1:1 to receive either 200 mg of pembrolizumab every 3 weeks for 1 year (maximum 18 doses) or placebo every 3 weeks for 1 year (maximum 18 doses). Eligible participants included patients with stage IB to IIA NSCLC who had received prior surgical resection (either lobectomy or pneumonectomy). DFS was calculated as the time between randomization and the date of either disease recurrence, occurrence of second lung cancer primary, occurrence of second primary, or death from any cause, whichever occurred first.

Pembrolizumab’s safety profile was found to be consistent with previously reported data. However, full results are expected to be represented at an upcoming medical meeting, as well as submitted to regulatory authorities for discussion.

Nursing considerations related to pembrolizumab include monitoring patients closely for symptoms for underlying immune-mediated adverse events (AEs). Liver enzymes, creatinine, and thyroid function should be evaluated at baseline and periodically assessed throughout treatment. In the case of a suspected immune-related AE, alternative etiologies, including infection, should be excluded via appropriate workup.

If interruption or discontinuation is necessary in response to an immune-related AE, systematic corticosteroid therapy should be administered at a dosage of 1 to 2 mg/kg daily until the AE improves to grade 1 or less. Other systematic immunosuppressants may be appropriate for patients whose immune-related AEs are not able to be managed through corticosteroid therapy. Furthermore, drug manufactures urge providers to be cognizant of the risk of colitis, hepatitis, and pneumonitis that can be associated with this immunotherapy.

“The goal of adjuvant treatment is to lower the risk of cancer returning after surgery,” co-principal investigator Luis Paz-Ares, MD, PhD, professor of medicine at Hospital Universitario 12 de Octubre in Madrid, Spain, said. “By moving [pembrolizumab] into earlier stages of non-small cell lung cancer, we may be able to reduce the risk of disease recurrence after surgery for patients with stage IB to IIIA non-small cell lung cancer.”

Merck’s KEYTRUDA (pembrolizumab) showed statistically significant improvement in disease-free survival versus placebo as adjuvant treatment for patients with stage IB-IIIA non-small cell lung cancer regardless of PD-L1 expression. News release. Merck; January 10, 2021. Accessed January 10, 2022. 

Articles

Pembrolizumab was associated with the first positive clinical trial outcomes in the adjuvant setting of non–small-cell lung cancer. 

Adjuvant Pembrolizumab Yields Impressive Disease-Free Survival Outcomes in Select Patients With NSCLC

Patients with lung cancer who quit smoking at or around their cancer diagnosis may be able to improve their rate of survival, according to a meta-analysis published in 

Furthermore, the data suggest that smoking cessation education and support is vital even after diagnosis.

Specifically, the findings revealed that patients who successfully stopped smoking improved their overall survival (OS). These findings were consistent across different subtypes, including patients with non–small cell lung cancer (summary relative risk [SRR], 0.77; 95% CI, 0.66-0.90, n studies = 8), small cell lung cancer (SRR, 0.75; 95% CI, 0.57-0.99; n studies = 4), or lung cancer of both or unspecified histological type (SRR, 0.81; 95% CI, 0.68-0.96; n studies = 6).

In the meta-analysis, smoking cessation was defined as ceasing to smoke either at moment of diagnosis, during treatment, or in the 12 months leading up to the diagnosis.

“Lung cancer remains a disease with poor prognosis despite recent advances in treatments. Here, we aimed at summarizing the current scientific evidence on whether quitting smoking at or around diagnosis has a beneficial effect on the survival of [these] patients,” lead investigator Saverio Caini, MD, of the Institute for Cancer Research, Prevention and Clinical Network in Florence, Italy, and colleagues, said.

“Our study suggests that treating physicians should educate patients with lung cancer about the benefits of quitting smoking even after diagnosis and provide them with the necessary smoking cessation support,” Caini added in a news release.

Researchers analyzed articles published between 1980 and October 31, 2021 via MEDLINE and EMBASE and successfully identified 21 evaluable articles, which quantified the impact of smoking cessation and patient survival in lunger cancer. Among these articles, over 10,000 patient cases were examined.

In the study, the authors note that there are different biological mechanisms related to tobacco that may explain these findings and provide a basis for further research. For example, tobacco use is associated with tumor growth, progression, and dissemination. It is also linked to reduced efficacy in radiation and systematic therapy, as well as a reduction in tolerance to therapy. Lastly, tobacco use has been observed to increase the risk of postoperative complications and second primary cancers.

Study authors also noted that systematic differences could factor into the findings, explaining that between patients who ceased to smoke and those who did not, variables in demographics, tumor characteristics, and disease stage may also contribute to OS rates. Furthermore, patients who can quit may be at an increased likelihood of undergoing resection with curative intent.

“The meta-analysis has implications beyond clinical practice,” Caini concluded. “Since heavy smokers would be primarily targeted by lung cancer screening programs, screening could serve as a teachable moment to help participants quit smoking by integrating a structured cessation program into the screening activities.”

Caini S, Riccio MD, Vettori V, et al. Quitting smoking at or around diagnosis improves the overall survival of lung cancer patients: a systematic review and meta-analysis. 

Published onlineJanuary 4, 2021. Accessed January 5, 2021.doi:10.1016/j.jtho.2021.12.005

Smoking Cessation After Cancer Diagnosis Associated With Improved Survival. International Association for the Study of Lung Cancer. News release. January 4, 2021. Accessed January 5, 2021. https://bit.ly/3JMiAH1

New data support smoking cessation for patients with lung cancer following their diagnosis. 

Smoking Cessation Following Lung Cancer Diagnosis Reduces Cancer Mortality Risk 

The implementation of the International Association for the Study of Lung Cancer (IASLC)’s language guide represents a paradigm shift in intentional language use in lung cancer. The guide, which prioritizes patient-first, blame-free, stigma-free, and culturally sensitive language, is intended to help guide best practices for all written and spoken materials submitted for abstracts and presentations at World Lung Cancer conferences.

It is important to note that the publication represents best-practice guidelines and not an exhaustive “do” or “don’t” list. It is hoped that evolving the language used by medical professional can help alleviate the potentially hurtful statements that patients living with lung cancer sometimes encounter throughout their journey.

The project was spearheaded by Jill Feldman, who is chair of the IASLC Patient Advocate Committee, and a Chicago native living with lung cancer.

“Over time, the patient voice has become more valued and more credible,” said Feldman, in a press release. “And we are really trying to help medical professionals and scientists understand that our input will make their research, its results, and their treatments more relevant to patients.”

Feldman collaborated with Jamie Studts, PhD, from the University of Colorado’s Medical Oncology Division, in Boulder, Colorado, and Jamie Ostroff, PhD, of Memorial Sloan Kettering Cancer Center in New York, New York, to develop the IASLC Language Guide.

Studts noted that adjusting language is a “cost-free” measure that can play a critical role in patient healing.

The guide focuses on 4 simple areas of language growth. The first area is an emphasis on “patient-first language.” The intention behind this change is put the person before the disease, literally, and to avoid defining people by their disease. Therefore, IASLC supports phrases such as “patient or person with lung cancer” instead of “lung cancer patient.” Similarly, when discussing clinical trials, “patient,” “person,” and “participant,” are preferred or over the word “subject.” IASLC also supports the phrase “patient with active tobacco use” instead of the word “smoker.”

“We are not and should not be defined by our disease,” explained Feldman. “We are not solely the disease; we are so much more.”

The second focus area is to eliminate “blame language.” Some words that are rooted in medical history have the tendency to feel judgmental. IASLC supports creating a more inclusive environment by prioritizing words that are more empathetic and non-judgmental. Phrases such as “unable to” or “not able to” may be a better choice than “non-compliant.” Similarly, “cancer progressed” is preferred over “patient progressed” and “treatment failed patient” is preferred over “patient failed treatment.” The phrase “chief concerns” is thought to sound more empathetic than “chief complaint.” Moreover, the phrase “risk reduction” is believed to be individual patient-centered compared to “prevention” which is population-centered. Risk reduction is therefore more aligned with the current communication direction of personalized medicine.

The third focus area concentrates on ending stigmas. The medical community has become aware that as aggressive public health policies and messages attempt to de-normalize smoking, there has been an increase in judgement towards those who have or currently smoke. Consequently, the intention behind these stigma-free language changes is to promote judgement-free, bias-free language instead of categorizing people by behaviors.

The guide suggests trying the phrase “person who smokes” and “person who doesn’t smoke” instead of “smoker” and “nonsmoker” as well as using the phrase “person with smoking history/exposure” instead of “former smoker.” Furthermore, the guide supports the use of the phrase “person with nicotine dependence” instead of “nicotine addict.”

“Society tends to believe that lung cancer is about tobacco, meaning that people do this to themselves, so they do not deserve our support and compassion,” noted Studts. “They know that the disease is “a devastating illness and people die, which can lead to fatalism, pessimism, and just a real sense of futility.”

Respectful and considerate language is therefore essential to improving overall patient care, he added.

Lastly, the guide notes that language plays an important role in promoting equity among the lung cancer community. Respectfully language in this capacity includes cultural humility and sensitivity in light of race, ethnicity, gender, socioeconomic, and geographic descriptions.

“The language we have been using does not allow a more complex story to emerge about people's real experiences, and that tends to isolate and alienate the very people we are trying to help,” summarized Studts. “And, that stigma has impacted policy and the allocation of research dollars and funding over time.”

“This is an incredible milestone and an acknowledgement of the importance of patients and academics forming partnerships for change,” added Ostroff. “The next step is to move it to the international stage, so there can be global improvement in ending the stigma of lung cancer.”

Ostroff expressed that, for her, the most important aspect of the guide was that it was created alongside patient advocates.

“We came together from different places, with different methods and different training, but we all agree that words matter, and that it is possible to change the language we use to talk to and about persons with lung cancer, as well as about people who use tobacco,” Ostroff said. “And we can do that in a way that that conveys respect, inclusivity, and equity.”

Language Guide. IASLC. May 2021. Accessed January 3, 2022. 

IASLC Releases the IASLC Language Guide: A Lexicon of Healing for Lung Cancer and Beyond. IASLC. News release. July 2, 2021. Accessed January 3, 2022.

Patient advocate Jill Feldman led the development of the language guide to help promote patient-centered, stigma-free language across the lung cancer community. 

IASLC Releases Language Guide to Promote Stigma-Free Discourse

Fast-mimicking dieting (FMD) was found to be safe, feasible, and potentially beneficial for patients with various solid tumor types and who were receiving different anticancer therapies, according to a study published in 

. The diet, which involved short-term, severe caloric restriction was associated with a decrease in blood glucose and growth factor concentration, as well as a reduction in peripheral blood immunosuppressive cells, and enhanced intratumor T-cell infiltration, among this population.

Among 99 evaluable participants, the median plasma glucose concentration reduction was 18.6%, the serum insulin reduction was 50.7%, and the serum IGF-1 reduction was 30.3%. Throughout the 8 consecutive cycles, these results remained consistent.

“Our results from a first-in-human clinical trial showed that a scheme of severe short-term calorie restriction was safe and biologically active in patients, and that its activity likely involved the activation of immune responses,” said co-author Claudio Vernieri, MD, PhD, Fondazione IRCCS Istituto Nazionale dei Tumori and the director of the Metabolic Reprogramming in Solid Tumors program at the FIRC Institute of Molecular Oncology, in Milan, Italy, in a press release. “Since calorie restriction is a safe, inexpensive, and potentially effective approach that could be easily combined with standard antineoplastic therapies, we think these findings might have relevant implications for cancer therapy.”

The study assessed a total of 101 patients. These participants had a variety of tumor types and were receiving various standard anticancer therapies. The global compliance rate among these participants was 91.8%; compliance in this case was defined as observing all 8 FMD cycles.

The most common adverse event (AE) associated with the dieting technique was fatigue and was rarely severe (12.9%). Thus, the trial met its primary safety end point.

The diet itself involved the following cycle: 5-days of low-carbohydrate, low-protein, plant derived dieting amounting to a total of 1800 calories (600 calories on day 1 and 300 calories on the subsequent 4 days). This cycle was followed by a period or regular eating for about 3 to 4 weeks and followed by another cycle. The study period involved 8 total cycles. When patients were not observing the FMD cycle, they were not restricted to any dietary regulations, but were encouraged to adhere to a healthy diet and lifestyle.

The loss of body weight that occurred during the 5 days of severe calorie restriction was reversible in most of the patients during the refeeding period.

“This is an especially important finding, because it excludes the risk that patients might undergo progressive weight loss and/or malnourishment, which are associated with reduced efficacy of anticancer therapies and reduced survival,” added Filippo de Braud, MD, director of the Oncology and Hematology Department of Fondazione IRCCS Istituto Nazionale dei Tumori and professor of medical oncology at the University of Milan in Milan, Italy.

Researchers determined that at the conclusion of the 5-day restricted calorie diet, patients had a significant decrease in circulating immunosuppressive myeloid subpopulations and an increase of activated CD8+ T cells. Notably, the various concomitant antitumor therapies did not impact these results. Additionally, a group of cancer-free volunteers also produced the same effects.

To corroborate the findings, researchers also performed an interim analysis of another ongoing trial (DigesT; NCT03454282). Patients in this trial were asked to complete a 5

day FMD cycle 7 to 10 days before undergoing surgery for early-stage breast cancer or melanoma. The tumor-infiltrating immune cells and transcriptomic immune profiles revealed a significant increase in tumor-infiltrating CD8+ T cells and other changes, suggesting that FMD induces an antitumor immune microenvironment.

The study authors concluded that the experimental diet generated favorable immunomodulatory effects at both the systematic and the tumor level. These findings indicate that a coherent immune response originates in the blood and consequently propagates to the tumor.

The main study limitations are related to the heterogeneous nature of the participants; because the patients all had different tumor type and concomitant anticancer therapies, researchers could not conclude the antitumor efficacy of the caloric restriction.

Consequently, the authors have helped to launch a series of new clinical trials, including the BREAKFAST trial (NCT04248998), which will seek to better understand the antitumor effects of the FMD diet among patients with solid tumors. Researchers hope to uncover ways in which diet and caloric restrictions may improve the potency of antineoplastic therapies and potentially prolong the life expectancy of patients in this population.

Fasting-mimicking diet is safe, may modulate metabolism and boost antitumor immunity in cancer patients. American Association for Cancer Research. News release. November 17, 2021. Accessed November 29, 2021. https://bit.ly/3ELIaZS

Patients with various solid tumor types experienced improved antitumor immunity after adhering to a diet with severe caloric restrictions.

Fast-Mimicking Diet Is Potentially Beneficial for Patients With Solid Tumors

Although surgery is an option for some patients with lung cancer, unmet needs related to postoperative recovery can negatively affect a patient’s quality of life and increase the family caregiver’s burden, explained Virginia Sun, PhD, MSN, RN, associate professor in the Division of Nursing Research and Education at City of Hope, a cancer research and treatment organization near Los Angeles, California.

To address these needs, Sun and her colleague, Jae Kim, MD, assistant professor and chief of the Division of Thoracic Surgery at City of Hope, launched a 5-year study in 2018 focusing on how to best support family care-givers after a loved one has undergone surgery for lung cancer. Sun and Kim developed the study after working on a previous research project that showed although standard intervention and education methods, such as videos and printed materials, were helpful for patients, they weren’t as helpful for caregivers.

Sun’s study examines the differences between a caregiver control arm that receives traditional education materials and one that receives these materials as well as face-to-face sessions with an oncology nurse to help address specific patient and caregiver needs and problems.

Although some oncology centers have nurse navigators that work with family caregivers, that isn’t the case with all medical centers. Sun said it’s important for all oncology nurses to ensure good outcomes for patients with lung cancer by ensuring their caregivers are well prepared.

With an increase in minimally invasive surgery for lung cancer, the length of hospital stays has decreased, with patients now typically spending 2 to 3 days in the hospital after minimally invasive surgery. Although many patients prefer to recover at home, Sun said when caregivers aren’t adequately prepared, patients with lung cancer can experience complications that result in being readmitted to the hospital.

Caregiver preparation often consists of videos and print materials developed by groups, such as the American Society of Clinical Oncology. Although those resources are informative, caregivers often need more personalized support, Sun said.

“Oncology nurses can help families and family caregivers by simply asking them about their needs and how they are doing,” she said. “Many family caregivers report they’ve never been asked about their needs. A simple question can lead to improved assessment, provision of relevant information, and referrals for support to families.” Sun recommended that oncology nurses determine who will be the primary family caregivers for a patient, and whether there will be more than 1 family member taking on this role, and assess their knowledge needs and caregiving preparedness. “Most family members are interested in how they can better prepare for the day of surgery and the recovery process, and what to expect during these times,” Sun said. “If possible, nurses can think about how we can best use the preoperative period to educate and prepare families for what’s ahead and to also encourage care- givers to think about their own self-care plan, as many family caregivers may be coping with their own illness.”

Shayne Cardozo, RN, nurse coordinator for the thoracic surgery and oncology clinic at the University of California, San Francisco Health, works with many patients with lung cancer and their family caregivers and strives to give them the information and support they need after they’re discharged from the hospital. “The quality of life for these patients with lung cancer should be the same or better after surgery,” Cardozo said. “We stress an active recovery where, after receiving approval from their doctor, they engage in walking and deep breathing exercises. The more they can do, the faster they will recover.”

In addition, Cardozo demonstrates how to properly use devices, such as an incentive spirometer, so patients can expand their lungs to help them breathe more deeply and fully. Doing this, as well as regular breathing and coughing exercises, also helps patients to keep their lungs active during their recovery and prevents complications, such as pneumonia.

Cardozo also works with patients to develop a personal plan to treat postsurgery pain and address common adverse events, such as constipation caused by pain medications. “At-home patients tend to fall behind on their pain medications,” she said. “Many are fearful they will become addicted to pain medications, so it’s important to let them know prescription opioids are generally safe when prescribed by their doctor and taken for a short period of time.”

Cardozo sees the role of a family caregiver as that of a personal trainer who offers encouragement and support to their loved ones by ensuring they follow postoperative instructions, take their medications, and practice breathing exercises. She also advises care- givers to call her in the event they have questions or if their family member experiences a fever, discharge from the incision site, chest pain, or shortness of breath.

Sometimes the most important tool that oncology nurses can provide caregivers is reassurance. “Caregivers need to feel empowered that they are part of the health care team and have the tools and answers in place to care for their loved one,” Cardozo said. 

Prieto R, Ferrell B, Kim JY, Sun V. Self-management coaching: promoting postoperative recovery and caregiving preparedness for patients with lung cancer and their family caregivers. 

. 2021;25(3):290-296. doi:10.1188/21.CJON.290-296

As minimally invasive surgery for lung cancer increases in popularity, more patients are recovering at home, expanding the need for personalized caregiver education.

The Oncology Nurse’s Role in Preparing Patients and Caregivers for Postoperative Recovery

Patients with lung cancer, especially patients with minimal serologic response following a second dose of the SAR-SoV2 vaccine, safely experienced seroconversion after receiving a third dose of the vaccine, according to findings from a French study published in the 

The results showed that most patients were immunized after 2 doses and that a third booster shot given to 11% of patients who had persistent low antibody titers induced an 88% immunization rate.

“Though lung cancer patients were reported at high COVID-19-related mortality risk in published series, lethality systematically exceeding 30% of infected patients, we observed only 8 mild COVID-19 cases among our 306 vaccinated patients (2.6%). Such observation strongly supports the efficacy of mRNA COVID-19 vaccines used in 98.4% of our population,” lead study authorValérie Gounant, MD, of the University Hospital Bichat-Claude Bernard in Paris, France, and coauthors wrote in the study publication.

In January 2021, COVID-19 vaccines were made available in France. To increase access to the first vaccine dose, the French Health authorities recommended a 28-day interval for both mRNA vaccines, with a 42-day interval for healthy individuals.

Despite the high COVID-19 mortality rate among patients with lung cancer, the population was excluded from SARS-CoV2 vaccine registration trials, leaving it unknown whether they could develop a protective anti-spike antibody response after vaccination.

As such, investigators conducted a study to evaluate the humoral responses to SARS-CoV2 vaccines in patients with thoracic malignancies.

The prospective study included patients with thoracic cancers who had been seen in Bichat Hospital from January 26, 2021 to July 28, 2021. Patients who had been diagnosed with thoracic cancer and had no known COVID-19 infection within the past 3 months, a life expectancy greater than 3 months, and no known allergies to prior vaccines were contacted and offered vaccination.

The investigators enrolled and vaccinated 306 patients with lung cancer. Most patients were male (n = 181; 59.2%) and had lung cancer (n = 285; 93.1%); 260 patients (84.9%)

had non–small cell lung cancer and 22 (7.2%) had small cell lung cancer, while 13 patients (4.4%) had pleural malignant mesothelioma. Patients were a median age of 67 years (interquartile range, 58-74), and the majority (n = 283) had received 2 vaccine doses at 28-day intervals.

The last treatment patients received within 3 months before their first vaccine dose was chemotherapy (n = 74; 24.2 %) alone (n = 51; 16.7%), with concurrent radiotherapy (n = 2), or combined with a checkpoint inhibitor (n = 21; 6.9%); 49 patients (16%) received a checkpoint inhibitor alone, and 13.7% were treated with daily TKIs or maintenance bevacizumab (Avastin). The last 141 patients (30.7%) had not received systemic treatment within the last 3 months leading up to vaccination.

The primary end point was the humoral immunity against SARS-CoV-2-spike following the COVID-19 mRNA BNT162b2 vaccine injection and booster dose. Some patients were vaccinated outside the center and received the Moderna mRNA-1273 (n = 1) or AstraZeneca ChAdOx1 nCov-19 (n = 3) vaccines.

SARS-CoV2-spike antibodies were measured with the Abbot ARCHITECT SARS-CoV-2 IgG immunoassay before the first injection of the mRNA vaccine, after the fourth week, and 2 to 16 weeks after second vaccine dose.

After a median follow-up of 6.7 months, 8 patients (2.6%) had developed symptomatic SARS-CoV-2 infection, with a fast-onset evolution. Of 269 serological results that had been collected after 14 days following the second vaccine dose, 17 (6.3%) were still negative (<50 arbitrary units [AU]/mL), and 34 (11%) were less than 300 AU/mL in the 12.5th percentile—the level at which an exact correlation was found between anti-S antibodies and neutralizing antibodies.

Multivariate analysis demonstrated that age, chemotherapy as the last systemic treatment within 3 months, and chronic corticosteroid treatment were significantly associated with a lack of immunization.

Thirty patients received a third vaccine dose, after which 3 patients showed persistent negative serology and the rest seroconversion.

In terms of safety, data were available for most patients (n = 278; 90.1%), without significant safety concerns.

One-third of patients (n = 98) did not report symptoms following their first injection. Reported adverse effects (AEs) included transitory pain, injection-site swelling, or grade 1 injection-site erythema lasting less than 24 hours.

AEs were reported in 201 patients following the second dose and included injection-site erythema, pain, local injection-site swelling, mild fever (< 38.5°C) all lasting less than 36 hours. Flu-like symptoms, chills, and fatigue lasting less than 48 hours were reported in 25 (8%) cases.

Additionally, no anaphylaxis reaction was reported following the administration of 587 vaccine doses.

“Although this report involves, to the best our knowledge, the largest series of patients [with thoracic cancer] receiving anti-SARS-CoV-2 mRNA vaccines that has been published to date, the sample size of the different patient subsets remains limited,” the authors concluded.

Gounant V, Ferre VM, Soussi G, et al. Efficacy of SARS-CoV-2 vaccine in thoracic cancer patients: a prospective study supporting a third dose in patients with minimal serologic response after two vaccine doses. 

COVID-19 vaccine effective in patients with lung cancer results from a French study published in the Journal of Thoracic Oncology. News release. IASLC. November 16, 2021. Accessed November 19, 2021. https://bit.ly/3HCNZdX

This article was originally published on OncLive as “Third SARS-CoV2 Vaccine Shows Evidence of Seroconversion in Lung Cancer”

A study in France showed that patients with lung cancer, a population initially excluded from COVID-19 vaccination registration trials, were able to safely receive 3 doses. 

Third COVID-19 Vaccine Dose Effective and Safe in Patients with Lung Cancer

Adults whose insurance covers lung cancer screenings were more likely to receive invasive screening procedures than patients in clinical trials, according to a study published in the 

. However, the out-of-pocket costs associated with downstream procedures may discourage adults with abnormal results to pursue their follow-up tests.

Among a group of 6,268 national employer-insured adults who received at least 1 low-dose CT scan (LDCT), 462 individuals (7.4%) followed up with a secondary or downstream procedure within the 12 months following screening.Women (adjusted odds ratio [aOR], 0.82; 95% CI, 0.68-0.99) and adults over the age of 65 (aOR, 1.62; 95% CI, 1.28-2.04) were more likely to follow-up with a downstream procedure.

The most common downstream procedure was a needle biopsy (69.0%), followed by cytology (23.6%), bronchoscopy (18.6%), and surgery (23.8%). A total of 93 patients (20.1%) received a lung cancer diagnosis following screening.

Overall, lung screening for this population costs $5,060,511.04 (an average of $740.06 perpatient). In comparison, the total out-of-pocket cost with this population was $427,069.74 ($62.46 per person.)

“[Out-of-pocket] costs associated with follow-up testing represents an underdiscussed risk, and the SDM should include patient financial consequences,” explained Tina D. Tailor, MD, Duke University Medical Center, Department of Radiology, and colleagues, in the study. “Given the existing disparities in lung cancer incidence and outcomes which cause disproportionate burden to vulnerable populations, failure to comprehensively address costs associated with [lung cancer screening] may disincentivize or discourage screening and/or necessary follow-up testing for certain populations. This may inadvertently widen existing lung cancer disparities.”

In 2010, the Patient Protection and Affordable Care Act (PPACA) was enacted. This requires non-grandfathered private and commercial insurers to cover USPSTF Grade A and B recommendations without cost-sharing. In addition, Medicare and most state Medicaid programs cover annual lung cancer screening with LDCT. Consequently, there has been a steady uptake in screening utilization since 2013.

In this study, researchers retrospectively analyzed data collected from patients between the ages of 55 and 79 who received screening between 2015 and 2017, noting the types and frequencies of downstream invasive procedures. Researchers then determined total costs per-episode (defined as a lung cancer screening exam and downstream procedure) and out-of-pocket costs using linear and logistic regression. Findings did not reveal an association between downstream procedures and race/ethnicity, poverty level, geographic division, or health plan type.

The out-of-pocket cost increased with each downstream procedure. The cost for these procedures managed between $0 and $342.05 with a median cost of $50.79. Of the 466 patients who received at least 1 follow-up procedure, 61% experienced an out-of-pocket cost.

Patients who received a lung cancer diagnosis at their consequent procedure paid an average of $332.24 and out-of-pocket costs for patients in this population ranged between $0 and $1,341.52. Those who did not pursue a downstream procedure after their screening did not experience out-of-pocket costs.

Notably, patients living in the Pacific region were more likely to have 0 out-of-pocket costs in comparison to patients in the East northern Central Region (OR, 1.67; 95% CI, 1.26-2.22). Patients living in the West-South Central Region were the least likely to have 0 out-of-pocket costs (OR0.76; 95% CI, 0.61-0.95).

Health plan types also impacted patient costs. Zero costs were associated with POS and PPO (OR, 0.67; 95% CI, 0.57-0.80) plans as opposed to HMO plans (OR, 0.49; 95% CI, 0.29- 0.83).

“Even a small [out-of-pocket] cost can induce burden among the financially fragile, such as those living at or below the federal poverty level, necessitating trade-offs between paying their cost share and other household or health expenses,” the study authors concluded. “Innovative insurance design needs to align insurance premiums or an [out-of-pocket] bundle covering the entire [lung cancer screening] episode to decrease the financial burden across the population of [lung cancer screening]-eligible individuals.”

Study authors acknowledged was limited by patients being required to have at least 12 months of continuous insurance coverage in 1 plan to be included. Consequently, patients switching insurances or who became uninsured during the study period were not included and therefore the procedural rates and costs may be underrepresented. Furthermore, the majority of included patients had POS health plans and the findings therefore may not be generalizable to other health plan types. Finally, costs did not consider procedure related complications. Further research should seek to address these factors to better assess the screening-related costs and expenditures.

Tailor TD, Bell S, Fendrick AM, Carlos RC. Total and out-of-pocket costs of procedures after lung cancer screening in a national commercially insured population: estimating an episode of care. 

J. American College of Radiology (accepted preproof). 

Available from: https://els-jbs-prod-cdn.jbs.elsevierhealth.com/pb-assets/Health%20Advance/journals/jacr/PreProofJACR_Manuscript_JACRAD-D-21-00091-1632519372147.pdf

A total of 7.4% of patients received a secondary or downstream procedure within the 12 months following their lung cancer screening.


Cost May Prevent Patients from Pursuing Procedures After Free Lung Cancer Screenings

Patients with extensive-stage small cell lung cancer (ES-SCLC) who received trilaciclib (Cosela) prior to receiving chemotherapy experienced reduced chemotherapy-induced myelosuppression, according to data 3 phase 2 trials (NCT02499770; NCT03041311; NCT02514447) published in 

Results showed that the administration of trilaciclib before chemotherapy significantly improved the incidence and duration of severe neutropenia (SN), defined as an absolute neutrophil count of less than 0.5 × 10⁹ cells/L, in cycle 1. Specifically, 11.4% of patients (n = 14) who received trilaciclib experienced SN vs 52.9% of those (n = 63) who received placebo (adjusted relative risk [aRR], 0.206; 95% CI, 0.120-0.351;

< .0001). The mean duration of SN was 0 days with trilaciclib compared with 4 days with placebo (

Fewer patients who received trilaciclib required granulocyte colony-stimulating factors (G-CSFs) compared with those who were given placebo, at 28.5% and 56.3%, respectively (aRR, 0.509; 95% CI, 0.371-0.700; 

< .0001). Moreover, 3.3% of patients receiving trilaciclib needed erythropoiesis-stimulating agents (ESAs) vs 11.8% of those receiving placebo (

= .0254); 14.6% and 26.1% of patients, respectively, required red blood cell (RBC) transfusions 

“Compared with placebo, trilaciclib consistently reduced the duration and occurrence of SN, regardless of G-CSF administration. This translated into a reduction in G-CSF administration compared with placebo,” lead study author Renata Ferrarotto, MD, of The University of Texas MD Anderson Cancer Center, wrote. “Trilaciclib also consistently reduced the occurrence of chemotherapy-induced anemia, which was reflected in the reduction of RBC transfusions on/after week 5 and ESA use. By improving key myelosuppressive end points and reducing the need for associated supportive care, trilaciclib has the potential to reduce both the societal and economic burden of CIM.”

Standard-of-care (SOC) approaches for patients with ES-SCLC, such as carboplatin plus etoposide (E/P), E/P plus atezolizumab (Tecentriq), E/P plus durvalumab (Imfinzi), and second-line lurbinectedin (Zepzelca) and topotecan are all known to result in significant CIM.

Chemotherapy dose delays and/or reductions can be used to manage CIM, as well as supportive care comprised of granulocyte-colony stimulating factors (G-CSFs), erythropoiesis-stimulating agents (ESAs), and RBC and platelet transfusions. However, delays and modifications can negatively impact the efficacy of treatment. More interventions are needed to reduce the incidence of CIN.

The CDK4/6 inhibitor trilaciclib has emerged as an option that can reduce the incidence of CIM, and the agent has been examined in the following 3 randomized, double-blind, placebo-controlled trials: G1T28-05, G1T28-02, and G1T28-03. For the analysis published in 

, investigators pooled findings from all 3 trials to examine the use of G-CSFs, ESAs, and RBC transfusions, and to evaluate the relationship between supportive care interventions and the myeloprotective benefits of the agent.

Patients included on the trials were at least 18 years of age, had confirmed ES-SCLC, measurable disease per RECIST v1.1 criteria, an ECOG performance status of 0 to 2, and acceptable organ function.

G1T28-05 enrolled patients with newly diagnosed ES-SCLC. Patients were given intravenous (IV) trilaciclib at a dose of 240 mg/m2 or placebo, before chemotherapy on days 1 to 3 of each 21-day cycle for up to 4 cycles; this was followed by maintenance treatment with single-agent atezolizumab.

G1T28-02 also enrolled newly diagnosed patients with ES-SCLC. Here, patients received IV trilaciclib at 240 mg/m2 or placebo before chemotherapy on days 1 to 3 of each 21-day cycle. G1T28-03 included those with previously treated ES-SCLC, who received IV trilaciclib at 240 mg/m2 or placebo before IV topotecan at 1.5 mg/m2 on days 1 to 5 of each 21-day cycle.

In the trials, administration of ESAs and primary prophylaxis with G-CSFs was prohibited in cycle 1; however, therapeutic G-CSF was permitted. In cycle 2 and beyond, ESAs and G-CSFs were allowed per standard guidelines. RBC and platelet transfusions were permitted throughout the trials, per investigator discretion.

Key end points included duration of SN in cycle 1, occurrences of SN, G-CSF administration, grade 3 or 4 anemia, ESA administration, and occurrence and number of RBC transfusion on, or after, week 5.

A total of 242 patients were included in the pooled datasets; 123 received trilaciclib and 119 received placebo. Baseline and disease characteristics were noted to be comparable between the treatment arms. However, slightly more male patients and current smokers were noted in the investigative arm vs the control arm.

Additional data from the analysis showed that fewer patients who received trilaciclib (20.3%) experienced grade 3 or 4 anemia vs those who were given placebo (31.9%; aRR, 0.620; 95% CI, 0.405-0.949; 

Moreover, the proportion of patients requiring RBC transfusions due to anemia was consistently lower in the trilaciclib arm vs the placebo arm. The rate of RBC transfusions in the placebo arm rose from 8.4% in cycle 1 to 14.3% in cycle 4, whereas the proportion of those on the investigative arm who required RBC transfusions remained relatively stable.

In addition to attempting to improve quality of life for patients with ES-SCLC by reducing the need for supportive care interventions, the study authors pointed to the economic burden such treatments can have on patients. In the paper, they cited an analysis of almost 350 patients with SCLC. Results had indicated that 49% of the patients received G-CSFs, 43% received RBC transfusions, and 4% received ESAs. Incremental annual costs per patient with grade 3/4 hematologic adverse effects were $63,245 for neutropenia and $28,152 for anemia.2

“Together with the results from the current analysis, these data suggest that administering trilaciclib prior to chemotherapy has the potential to reduce the burden of CIM on healthcare systems by reducing the use of supportive care measures and CIM-related hospital admissions,” the study authors concluded.

Ferrarotto R, Anderson I, Medgyasszay B, et al. Trilaciclib prior to chemotherapy reduces the usage of supportive care interventions for chemotherapy-induced myelosuppression in patients with small cell lung cancer: pooled analysis of three randomized phase 2 trials. 

. 2021;10(17);5748-5756. doi:10.1002/cam4.4089

Epstein RS, Krenitsky J, Weerasinghe RK, et al. Real-world burden of myelosuppression in patients with small cell lung cancer (SCLC): retrospective, longitudinal data analysis. 

. 2020;38(suppl 15):e19300. doi:10.1200/JCO.2020.38.15_suppl.e19300

This article was originally published on OncLive as “Trilaciclib Possesses Potential to Reduce Burden of Chemotherapy-Induced Myelosuppression in ES-SCLC”

Trilaciclib was associated with reduced chemotherapy-induced myelosuppression and the need for associated supportive care in patients with a subtype of lung cancer. 

Trilaciclib May Alleviate Chemotherapy-Induced Myelosuppression in Extensive-Stage Small Cell Lung Cancer

As multiple novel therapies have entered the arena as potential first-line options, the best practices for managing toxicities related to frontline targeted therapy and immunotherapy treatments in lung cancer remain to be determined, explained Antoinette Wozniak, MD, FACP, FASCO. In addition, certain treatments like antibody-drug conjugates (ADCs) and combination regimens will require careful data consideration and monitoring of patients in order to best manage potential treatment-related toxicities.

“We have to analyze [the data from] these trials and put into practice what is most important and what will work best for patients. We need to be careful with some of these new agents in terms of adverse effects [AEs] and balance the delivery of the agents with toxicity,” Wozniak, a visiting professor of medicine, associate director of clinical research at the University of Pittsburgh Medical Center (UPMC) Hillman Cancer Center, director of the Lung Cancer Disease Unit, and co-director of the UPMC Lung Cancer Center of Excellence in the Division of Hematology/Oncology at UPMC, said in an interview with 

® during an Institutional Perspectives in Cancer (IPC) webinar on lung cancer.

“Everything that was discussed supports the importance of participation in clinical trials. Without those trials, we wouldn’t have these new agents. However, we need to be critical of the information and make sure that we don’t venture too far outside the box. We don’t know what some combinations might do in terms of toxicities,” Wozniak added.

Faculty who spoke during the virtual meeting covered frontline considerations with single-agent vs combination immunotherapy, targeted options against 

-mutated non–small cell lung cancer (NSCLC), and treatment options in small cell lung cancer (SCLC), as well as how to navigate the paradigm among novel targeted therapies directed toward 

In the interview, Wozniak spoke to the topics covered by her colleagues, highlighted the importance of monitoring patients with lung cancer for toxicities, and significant advances on the horizon that are expected to further expand the lung cancer armamentarium.

: What novel agents are emerging that you are intrigued by?

The ADCs are interesting, and a number of trials are ongoing [evaluating] ADCs. The whole idea is to identify a target. The agents [utilize] an antibody [directed] to the target, a linker, and a cytotoxic payload. It’s a fairly complicated process. ADCs have to be very specific so that they don’t cause significant systemic effects and that they get delivered primarily to the tumor. That is where we are heading in the future in terms of new agents.

 [are also emerging]. That will be interesting, particularly in the lung cancer paradigm, but not all of them work or have acceptable safety profiles. For example, an ADC called rovalpituzumab tesirine [was tested] in SCLC, but didn’t work and was fairly toxic. We have a lot of work to do with these agents, but they represent some of the more interesting agents.

Also of interest are clinical trials [exploring] agents [to use] after patients progress on immunotherapy. That’s a huge space. When we have patients who progress on immunotherapy or patients who responded for a while and then progress, it is difficult to try to figure out what to do next. Several trials are looking at why patients progress. A few molecules are interesting, such as those that target TIGIT and LAG3, as well as CTLA-4, which is still of interest. This is an area in which we are going to see a lot of clinical trials and development of new agents.

During the IPC meeting, Liza C. Villaruz, MD, of the UPMC Cancer Institute, discussed frontline immunotherapy in NSCLC. How are you selecting between utilizing single-agent immunotherapy vs combination chemoimmunotherapy in the frontline setting?

: Regarding single-agent immunotherapy vs combination chemoimmunotherapy, we’ve been struggling [with what is best to choose]. Everyone likes the idea of using just one drug, but there are certain instances where we need [chemotherapy as well].

In patients with a PD-L1 status below 50%, the consensus right now is to use [chemoimmunotherapy]. Pembrolizumab [Keytruda] is FDA approved as a single agent, even in patients with a PD-L1 status of 1% to 49%. In that group, however, we feel we need more. In the over 50% group, a lot of [treatment selection] depends on the volume and aggressiveness of the disease. The survival curves [in the pivotal trials that evaluated immunotherapy] cross because it takes a little time for immunotherapy to work. Therefore, in patients who have what may be more aggressive disease or a high volume of disease, it may be worthwhile to combine chemotherapy with immunotherapy to get a better response earlier. That is where we are at.

The INSIGNA trial [NCT03793179] is ongoing, looking at sequencing, even in the 1% to 49% group. That trial may give us more information on how we can use single-agent [immunotherapy] vs combination [chemoimmunotherapy].

Shirish M. Gadgeel, MD, of the Henry Ford Health System, spoke to the frontline management of 

-mutated NSCLC. What considerations are you making when selecting between available ALK inhibitors in this patient population?

We have a couple of very active agents [for 

-mutated NSCLC]. We have alectinib [Alecensa], brigatinib [Alunbrig], and lorlatinib [Lobrena]. It’s hard to do cross-trial comparisons, so most of us use what we feel comfortable with. In the case of [

-positive disease], most people likely use alectinib because it was the first next-generation inhibitor to show benefit over crizotinib [Xalkori] and we feel comfortable with the safety profile of that agent.

We’ve seen increased use of brigatinib because the dosing is easier [than alectinib]. Also, there is at least a suggestion in trials that [brigatinib] is quite active [against] brain metastases. Then again, we can’t say one is better vs another, especially when the [activity] looks similar.

We are seeing that we can [use the agent] we feel comfortable with but sequencing them is a little more complicated because we really don’t [have data on how to do that]. More information about resistance mechanisms for ALK inhibitors [is emerging]. For instance, 

 G1202R mutations seem to be popping up occasionally. Lorlatinib has activity there, so many of us are using lorlatinib in the second-line setting right now. There is more to come in terms of [understanding] the best way to sequence ALK inhibitors.

Taofeek K. Owonikoko, MD, PhD, of the UPMC Cancer Institute, highlighted advances made in frontline SCLC. What were some of the key points from his presentation that apply to clinical practice, and what is next for the field of SCLC?

SCLC is still very difficult to treat, so we have a lot of work to do. Dr Owonikoko was quite clear about that.

We saw the first advance in probably 20 years with the addition of immunotherapy to [chemotherapy in] extensive-stage disease. [In] World Series [speak], this was a base hit, not a home run. There was improvement [with the addition of immunotherapy], but it is difficult with SCLC because we don’t have any biomarkers. It’s a very complicated disease with a lot of mutations and abnormalities but not 1 driver mutation. We have to understand the disease to be able to divide it up into subtypes. Within the subtypes, we will hopefully be able to determine which patients are more likely to respond to immunotherapy vs some of the other drugs that are being [evaluated].

In terms of limited-stage SCLC, we have to wait for the results of clinical trials before we incorporate the use of immunotherapy [into the paradigm].

Finally, Timothy F. Burns, MD, PhD, of the UPMC Cancer Institute, spoke to recent advances with targeted therapy for patients with 

 mutation–positive NSCLC. How has your experience been with the novel targeted options, and what considerations should be kept in mind when utilizing the agents in clinical practice?

 mutations] are relatively new, so we don’t know how successful they are going to be in common clinical practice. They are excellent [additions] because 

 mutations have been very difficult to drug. I used to call them undruggable targets.

 exon 20 has been very frustrating because we see such good results when we treat exons 19 and 21. However, now we have 2 drugs [for patients with these mutations]. I have used both of these agents on expanded access. Both agents are approved as second-line treatments, so patients generally get chemotherapy first with or without immunotherapy.

Mobocertinib [Exkivity] is one of those drugs. It is oral, so it has that advantage. It’s a small molecule TKI. We have to be aware of the [AEs associated] with that drug, including gastrointestinal toxicities like diarrhea. Patient education with regard to the development of diarrhea and nausea is important to manage AEs. We also have to follow the recommendations for dose reduction. [Mobocertinib] does cause QT prolongation, so we have to be careful which drugs are combined with it. That is for not only anti-nausea agents, but also other drugs patients might be on. [As an example,] a patient [I treated] was on medication for anxiety and depression, some of which cause QT prolongation. We have to be really careful and monitor patients.

Amivantamab-vmjw [Rybrevant] is the other drug [approved for patients with 

 exon 20 insertion mutant–NSCLC]. It is a bispecific antibody [directed against] 

 that is given intravenously. At the initial time we give the drug, we see a lot of infusion-related reactions, so we must be cognizant [of those events]. They usually happen with the first infusion and is why the infusion is split over 2 days. [These reactions] don’t tend to happen later, but they can be fairly significant initially.

It wouldn’t be a bad idea to pre-treat patients [who will be receiving amivantamab] with steroids and H2 blockers, such as famotidine, and of course, diphenhydramine [Benadryl]. Pretreatment is important.

[Mobocertinib and amivantamab] are approved as second-line treatments, so which one is better? Which should we use? It’s dealer’s choice; one isn’t better than the other. They haven’t been compared directly. The toxicities are different so we have to consider that. If a patient wants to try an oral drug vs an IV [intravenous] drug, that might make our decision.

 mutations represent the most common mutation, [occurring in] approximately 25% of adenocarcinomas. They are very rare in squamous cell [carcinomas]. Although 

 was discovered a long time ago, we have not been able to target it. Now we have 1 drug available: sotorasib [Lumakras]. We also have 1 drug, adagrasib, in clinical trials, which is probably going to be approved soon.

Some of the toxicities to be aware of with sotorasib include diarrhea, some skin toxicities, and liver toxicities, which I ran into [with a patient]. We have to monitor patients carefully, but sotorasib seems to be reasonably well tolerated. The response rate is just around 37%, and the drug is being used in the second-line setting. The response rate is not as high as we see with ALK and EGFR inhibitors though.

First-line trials are planned [with sotorasib], likely in combination with chemotherapy or immunotherapy. We will see where this drug lands in the future, but for now, it is a second-line agent that has some activity. It’s reasonable to try sotorasib, or if we can [enroll patients onto] clinical trials, that’s the way to go.

 mutations] are being evaluated in clinical trials.

Antoinette Wozniak, MD, FACP, FASCO, outlines the importance of careful patient monitoring in lung cancer and emerging therapy options expected to change the treatment landscape. 

Lung Cancer