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”

Articles

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. 

Careful Patient Monitoring Critical in Emerging Lung Cancer Treatments

The addition of sintilimab (Tyvt) to chemotherapy significantly improved progression-free survival (PFS) among patients with 

-mutated, nonsquamous non–small cell lung cancer (NSCLC) who disease progressed following EGFR TKI-targeted treatment. Sintilimab, a novel bevacizumab biosimilar injection (Byvasda), thus met the primary end point of the phase 3 ORIENT-31 trial (NCT03802240), leaving researchers optimistic about the future of nonsquamous NSCLC treatment. 

Data from the first interim analysis, which were reviewed by the independent data monitoring committee and were based on an assessment by the blinded independent radiographic review committee (BIRRC), showed a statistically significant and clinically meaningful PFS improvement with the combination vs pemetrexed/cisplatin alone in the intent-to-treat (ITT) population.

Moreover, sintilimab in combination with chemotherapy also demonstrated a trend toward a PFS benefit vs chemotherapy alone, although the data are not yet mature.

Additionally, the prespecified PFS futility analysis comparing sintilimab plus bevacizumab biosimilar injection and chemotherapy with sintilimab plus chemotherapy was not found to cross the futility stopping boundary. The addition of the biosimilar to sintilimab and chemotherapy has a numerical benefit.

No additional safety signals were reported with sintilimab and bevacizumab biosimilar injection.

Detailed findings from the trial will be shared at an upcoming medical conference.

“ORIENT-31 is the first prospective, double-blind, phase 3 study worldwide to demonstrate significant PFS benefit with an anti–PD-1 antibody combination therapy in this patient population,” Professor Shun Lu, Oncology Department of Shanghai Chest Hospital, and principal investigator of ORIENT-31, stated in a press release. “It has shown the clinical value of adding sintilimab plus bevacizumab biosimilar injection to platinum chemotherapy. This quadruple regimen has the potential to bring forth a new and more effective treatment option to patients with 

-mutated nonsquamous NSCLC following treatment with an EGFR TKI.”

ORIENT-31 enrolled patients with disease progression following a first- or second-generation EGFR TKI who had either confirmed 

-positive disease but progression on a third-generation EGFR TKI treatment. The trial also enrolled those who experienced progressive disease after first-line treatment with a third-generation EGFR TKI.

Study participants were randomized 1:1:1 to receive intravenous (IV) sintilimab at 200 mg every 3 weeks plus bevacizumab biosimilar injection at 15 mg/kg every 3 weeks and pemetrexed at 500 mg/m2 every 3 weeks and cisplatin at 75 mg/m2 every 3 weeks or sintilimab plus placebo 2 combined with pemetrexed/cisplatin or placebo 1 plus placebo 2 plus pemetrexed/cisplatin.2

Following a total of 4 cycles of combination therapy, participants will go on to receive maintenance treatment with sintilimab plus bevacizumab biosimilar injection and pemetrexed, sintilimab plus placebo 2 and pemetrexed, or placebo 1 plus placebo 2 and pemetrexed. Maintenance treatment will continue until radiographic disease progression, intolerable toxicity, or any other conditions that necessitate treatment discontinuation.

The trial seeks to enroll 480 participants, and the primary end point is PFS per BIRRC and based on RECIST v1.1 criteria. Key secondary end points comprise overall survival (OS), investigator-assessed PFS, objective response rate, and safety.

Previously, in May 2021, a biologics license application for the frontline use of sintilimab injection plus pemetrexed and platinum-based chemotherapy in patients with nonsquamous NSCLC was accepted by the FDA for review.3

The application was based on findings from the phase 3 ORIENT-11 trial (NCT03607539), which indicated that the combination resulted in a significant improvement in PFS compared with chemotherapy alone in this patient population.4 At a median follow-up of 8.9 months, the IRRC-assessed median PFS in the investigative and control arms was 8.9 months (95% CI, 7.1-11.3) and 5.0 months (95% CI, 4.8-6.2), respectively (HR, 0.482; 95% CI, 0.362-0.643; 

The Chinese, double-blind, randomized phase 3 ORIENT-11 study examined the safety and efficacy of sintilimab plus pemetrexed and platinum-based chemotherapy as a frontline treatment in 397 patients with nonsquamous NSCLC.

Patients had to have stage IIIB/C or IV disease and not be eligible to undergo surgery or receive local therapy. They also needed to have an ECOG performance status of 0 or 1 and have a tumor sample available for PD-L1 assessment. Patients were stratified by gender, type of platinum therapy (cisplatin vs carboplatin) and PD-L1 expression level (tumor proportion score [TPS] less than 1% vs 1% or higher).

Participants were randomized 2:1 to receive either sintilimab at 200 mg (n = 266) or placebo (n = 131) in combination with pemetrexed at 500 mg/m2 and cisplatin at 75 mg/m2 or carboplatin at area under the curve (AUC) 5, every 3 weeks for 4 cycles.

Patients in the investigative arm received sintilimab at 200 mg every 3 weeks for up to 2 years; plus pemetrexed at 500 mg/m2 every 3 weeks; those in the control arm received placebo every 3 weeks for up to 24 months plus pemetrexed at the 500 mg/m2 every-3-week dosing schedule. Thereafter, patients on the control arm were permitted to cross over to receive sintilimab at 200 mg every 3 weeks for up to 24 months.

The primary objective of the trial was PFS per IRRC. Secondary end points included OS, response rate, duration of response (DOR), time to response, and safety. Efficacy was examined in the ITT population and safety data included all patients who received at least 1 dose of study treatment.

Additional data from the trial showed that PFS benefit correlated with PD-L1 expression level. The median PFS in patients with a TPS of less than 1% was 7.3 months (95% CI, 6.2–not reached [NR]) vs 5.1 months (95% CI, 4.6-7.8) with sintilimab and chemotherapy alone, respectively (HR, 0.664; 95% CI, 0.406-1.086). In those with a TPS of 1% to 49%, the median PFS was 7.1 months (95% CI, 6.2-9.2) and 4.8 months (95% CI, 2.5-8.0), respectively (HR, 0.503; 95% CI, 6.2-9.2). In those with the highest PD-L1 TPS of 50% or greater, the median PFS had not yet been reached (95% CI, 9.2–NR) with sintilimab vs 5.0 months (95% CI, 4.3-6.8) with chemotherapy alone (HR, 0.310; 95% CI, 0.197-0.489).

The addition of sintilimab was also found to result in an approximate 40% reduction in the risk of death vs chemotherapy alone, which was determined to be nominally significant (HR, 0.609; 95% CI, 0.400-0.926; 

= .01921). The 6-month OS rates in the investigative and control arms were 89.6% and 80.4%, respectively.

Moreover, the sintilimab combination induced an objective response rate (ORR) of 51.9% vs 29.8% with chemotherapy alone. The disease control rates achieved in the investigative and control arms were 86.8% and 75.6%, respectively. Time to response was shorter in the sintilimab arm vs the chemotherapy-alone arm, at 1.5 months and 2.6 months, respectively.

The most common toxicities included anemia, reduced neutrophil count, reduced white blood cell count, reduced platelet count, increased aspartate aminotransferase, increased alanine aminotransferase, nausea, reduced appetite, asthenia, vomiting, constipation, and pyrexia.

Innovent announces ORIENT-31, a phase 3 study of sintilimab in patients with EGFR-mutated nonsquamous non-small cell lung cancer with prior EGFR-TKI treatment, has met primary endpoint. News release. Innovent Biologics, Inc. October 17, 2021. Accessed October 18, 2021. 

Sintilimab +/- IBI305 plus chemotherapy (pemetrexed + cisplatin) for EGFRm + locally advanced or metastasis non-squamous NSCLC patients after EGFR-TKI treatment failure. ClinicalTrials.gov. Updated April 9, 2020. Accessed October 18, 2021. 

https://clinicaltrials.gov/ct2/show/NCT03802240

US FDA accepts regulatory submission for sintilimab in combination with pemetrexed and platinum chemotherapy for the first-line treatment of people with nonsquamous non-small cell lung cancer. News release. Innovent Biologics, Inc. May 18, 2021. Accessed October 18, 2021. 

Zhang Li, Yang Y, Wang Z, et al. ORIENT-11: sintilimab + pemetrexed + platinum as first-line therapy for locally advanced or metastatic non-squamous NSCLC. 

. 2020;15(10). doi:10.1016/j.jtho.2020.08.002

This article was originally published on OncLive as “Novel Sintilimab Combo Significantly Improves PFS in EGFR-Mutated Nonsquamous NSCLC”

Sintilimab, a bevacizumab biosimilar injection, met the primary end point of the phase 3 ORIENT-31 trial by significantly increasing progression-free survival in patients with EGFR-mutated, nonsquamous, non–small cell lung cancer. 

Sintilimab Plus Chemotherapy Induces Superior Survival in EGFR-Mutated Nonsquamous NSCLC

The FDA has approved atezolizumab (Tecentriq) as an adjuvant therapy to treat adults with stage II to IIA non-small-cell lung cancer (NSCLC) whose tumors harbor PD-L1, as demonstrated by an FDA-approved test, following resection and platinum-based chemotherapy, according to a press release by Roche.

The regulatory decision was informed by findings from an interim analysis of the phase 3 Impower010 study. Results demonstrated that atezolizumab therapy following surgery and platinum-based chemotherapy decreased the risk of disease recurrence or death by 34% (HR, 0.66; 95% CI, 0.50-0.88) among patients with advanced NSCLC and tumors with PD-L1 expression.

"[Atezolizumab] is now the first and only cancer immunotherapy available for adjuvant treatment of NSCLC, introducing a new era where people diagnosed with early lung cancer may have the opportunity to receive immunotherapy to increase their chances for cure,” Levi Garraway, MD, PhD, chief medical officer and head of global product development at Roche, stated in a press release. “Today’s landmark approval gives physicians and patients a new way to treat early lung cancer that has the potential to significantly reduce risk of cancer recurrence, after more than a decade with limited treatment advances in this setting.”

No new safety signals were detected. Among patients receiving atezolizumab, 1.8% experienced fatal adverse events (AEs) and 18% reported serious grade AEs. The most common AEs included pneumonia (1.8%), pneumonitis (1.6%), and pyrexia (1.2%). However, other toxicities included increased aspartate aminotransferase, blood creatinine, and alanine aminotransferase, as well as hyperkalemia, rash, cough, hypothyroidism, pyrexia, fatigue/asthenia, musculoskeletal pain, peripheral neuropathy, arthralgia, and pruritus.

“Too many patients with early-stage lung cancer experience disease recurrence following surgery. Now, the availability of immunotherapy following surgery and chemotherapy offers many patients new hope and a powerful new tool to reduce their risk of cancer relapse,” said Bonnie Addario, GO2 Foundation for Lung Cancer, sin the press release. “With this approval, it is more important than ever to screen for lung cancer early and test for PD-L1 at diagnosis to help bring this advance to the people who can benefit.

Notably, atezolizumab is also approved for genitourinary, skin, breast, gastrointestinal, gynecologic, and head and neck cancers. It is currently being evaluated as a monotherapy and in combination with other medicines across multiple different settings in solid tumors.

US FDA approves Roche's Tecentriq as adjuvant treatment for certain people with early non-small cell lung cancer. News release. Roche. October 15, 2021. Accessed October 15, 2021. 

Wakelee HA, Altorki NK, Zhou C, et al. IMpower010: primary results of a phase III global study of atezolizumab versus best supportive care after adjuvant chemotherapy in resected stage IB-IIIA non-small cell lung cancer (NSCLC). 

. 2021;39(suppl 15):8500. doi:10.1200/JCO.2021.39.15_suppl.8500

Atezolizumab is the first immunotherapy approved in the adjuvant setting to treat NSCLC.

FDA Approves Atezolizumab to Treat Select NSCLC in Adjuvant Setting

indicate that 6 months following the second dose of the Pfizer-BioNTech COVID-19 vaccine, patients with solid tumors and individuals without cancer displayed similar levels of COVID-19 antibodies in their blood.

Results from the study showed that 79% of those with solid tumors were seropositive for the antibodies compared with 84% of healthy controls at 6 months after their second dose of the vaccine. However, antibody levels in both groups decreased significantly from the time of vaccination.

“In our study we saw that in all outcomes, including immunogenicity, infectivity rate throughout the 6-month period, and safety, patients with solid tumors depicted a similar trend as the general population,” said lead study author Irit Ben-Aharon, MD, PhD, director of the oncology division at Rambam Health Care Campus in Israel.

Though the available COVID-19 vaccines have shown high efficacy in the general population, their long-term safety and efficacy among patients with cancer had been underrepresented. Moreover, patients with cancer receiving cytotoxic therapy or immune modifying agents were not able to participate in other vaccine studies, and as such, there remains an unmet need to examine the efficacy of the vaccines in this group.

Although it had been suggested that all patients with cancer were at increased risk for COVID-19 infection, recent studies have shown that outcomes and manifestations differ significantly depending on the malignancy type and treatment. Furthermore, data on vaccine efficacy in patients with cancer have shown similar short-term efficacy and safety among patients with when compared with healthy controls.

In this study, investigators sought to examine the long-term safety and efficacy of the COVID-19 vaccine in this population at 6 months after vaccination.

The study enrolled patients with solid tumors receiving active anti-cancer therapy and followed their progress for 6 months after the administration of the second dose of the vaccine. Patients must have been receiving their cancer therapy throughout 6-month duration, as well.

In the study cohort overall, investigators enrolled 154 patients with solid tumors, in addition to 135 age-matched healthy controls. Of the original cohort, 88 patients were enrolled; 64 who met the inclusion criteria were subsequently added.

In the solid tumor cohort, the median age was 66 years (range, 32-87), and more than half of patients were male (55%). In the control cohort, 56% of individuals were women and the median age was 63 years old (range, 50-87).

Most of the patients with cancer enrolled presented with metastatic disease (84%), and the most common cancer types were gastrointestinal (36%), lung (23%), breast (17%), and genitourinary cancers (11%). Moreover, the most common anti-cancer treatment among patients was chemotherapy (62%), followed by biological agents (36%) and immunotherapy (30%).

Additional data showed that chemotherapy was more highly associated with seronegative serologic status vs other treatment modalities (27% vs 10%; odds ratio [OR], 0.31; 

 = .02), and women were more likely to be seropositive than men (93% vs 75%; OR, 0.21; 

Furthermore, there was 1 documented case of severe COVID-19 infection that required hospitalization in the cohort of patients with cancer.

In terms of safety, elevation of liver enzyme levels was reported in 10% of patients with cancer up to 6 weeks after receiving the first dose of the vaccine. Moreover, newly documented regional lymphadenopathy was reported on 5% of CT/PET scans. However, all adverse effects were resolved in all patients throughout the course of the study period.

Additionally, the vaccination led to anti-cancer treatment delays for 6% of patients with cancer, all of whom were receiving chemotherapy. Delays were most commonly due to neutropenia, mild thrombocytopenia, and neutropenia with herpes labialis.

“Our study indicates that the pattern of immunogenicity and efficacy of the [Pfizer-BioNTech COVID-19 vaccine] in patients with solid tumors on active intravenous anti-cancer treatment 6-months post vaccination resemble the pattern of the general population,” the study authors concluded. “Former subtle differences which were evident between the 2 cohorts shortly after vaccination disappeared throughout time. Nonetheless, due to uncertainty of the extended efficacy of the vaccine in the general population and recent reports on rising infection rates among vaccinated individuals, adherence to health care risk reduction recommendations is cardinal.”

Waldhorn I, Holland R, Goshen-Lago T, et al. Six month efficacy and toxicity profile of BNT162b2 vaccine in cancer patients with solid tumors. 

. Published online September 2, 2021. doi:10.1158/2159-8290.CD-21-1072

Six-month efficacy of Pfizer/BioNTech COVID-19 vaccine in patients with solid tumors similar to general population. News release. American Association for Cancer Research. September 2, 2021. Accessed September 2, 2021.

The Pfizer-BioNTech COVID-19 vaccine induces similar levels of COVID-19 antibodies in patients with solid cancer compared with people without cancer.



COVID-19 Vaccine Elicits Similar 6-Month Antibody Response in Both Patients with Solid Tumors and the General Population

For this episode of “The Vitals,” we spoke with Martin Dietrich, MD, PhD, an assistant professor of internal medicine at the University of Central Florida, a fellow of the American College of Physicians, and a medical oncologist at Florida Cancer Specialists & Research Institute. Dietrich highlighted some recent advances and ongoing research in stage III non–small cell lung cancer (NSCLC) and discussed some of the ways immunotherapy and targeted therapy has evolved in recent years.

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“I think the biggest [change] that we’ve seen is the addition of adjuvant or consolidated chemotherapy following the completion of concurrent chemotherapy and radiation. We have seen the 4-year overall survival data now and the 5-year update from the PACIFIC study in the adjuvant setting, obviously confirming the initial signal that patients who have initiation of immunotherapy early carry a significant risk reduction for progression and overall survival…”

Expert Discusses Biggest Updates in NSCLC Treatment 

The ongoing phase 3 CheckMate-73L trial (NCT04026412) will appraise the safety and efficacy of nivolumab plus chemoradiation followed by nivolumab and ipilimumab (Yervoy) in patients with stage III non–small cell lung cancer (NSCLC) that is unable or not planned to be removed by surgery.

Oncology Nursing News® recently met with Sandra Duncan, RN, BSN, to discuss the potential ramifications of this trial for both nursing professionals and patients alike. Duncan is a clinical oncology research nurse who supports patients with cancer being screened or enrolled in clinical trials at the Georgia Cancer Center at Augusta University.

Although Duncan has worked as a nurse for 21 years at Augusta University, it wasn’t until recently that she made the transition to participating in clinical trial research. In this interview she also discussed how empowering and rewarding that career switch has been, as well as what her specific responsibilities have been in supporting the CheckMate-73L trial.

“I love it,” she began, at the beginning of the discussion. “I love what I'm doing. I feel like I am a connector for our potential subjects, working with our principal investigators and some other multi-specialty areas here at Augusta University with this particular study and, of course, the sponsor as well”.

 What has been your experience with the Checkmate 73L trial?

We had our site initiation visit in May of this year. We have yet to enroll the first patient, but our goal accrual here will be 4 patients over the next life of the clinical trial. I know we will meet that goal.

We have clinics on every Tuesday & Thursday. We also screen the patients that our other multidisciplinary physicians have, such as CT surgery, our radiation oncologist, and other medical oncologists. We actually screen their listing of patients. Since we have access to electronic health records (EHR), and since we can't meet all the patients, we screen based upon the eligibility and prescreen to see if they are potential patients at that time. … So, what we do is prescreen those clinics, and then we will, at that time, come up with any potential subjects before we actually have clinical or bring them in for clinic. So, we have an idea if that patient will meet eligibility requirements before being even approached at all.

We had 1 potential patient, unfortunately. I say unfortunately because when we got the referral, the patient already had received cardiothoracic surgery and was opted unresectable.

We use that as an educational piece to other multidisciplinaries and our tumor board to say, “This is the kind of patient that would have benefited from this type of clinical trial.” So, as we move forward, it's going to be continuing education, particularly because we have weekly tumor board meetings, where we talk about potential patients and re-education.

What are some of the unmet needs in NSCLC treatment right now?

I think what this particular clinical trial is simply going to do is give our patients more options. [If a patient says,] “I know I don't want surgery, then what else is out there for me?” That’s when we start discussing immunotherapy. I think that's one of the things that's needed for patients who do not opt to have surgery, many of them don't want to be in the hospital setting. This simply gives patients more options to have immunotherapy while doing radiation therapy than the 1-year maintenance treatment. That’s what is not available right now.

What are some of the challenges as that role of connecting the PI and all those moving components for a trial like this?

Sandra Duncan, RN, BSN, discusses her transition to clinical research, and what her responsibilities are like supporting the ongoing CheckMate-73L trial. 

Lung Cancer