Immunotherapy agents represent a transformational advance in our ability to treat many cancers. Rather than introducing a therapy that kills both healthy and malignant cells, immunotherapy agents harness the body’s natural ability to recognize and control the invasive cells that can form tumors.

Most patients who receive immunotherapies will experience few, if any, treatment-related adverse effects (AEs). But some patients receiving these treatments can experience serious AEs caused by an overactivation of the immune system and its effects on healthy cells.

It is important for clinicians to identify AEs quickly and assign such toxicities an appropriate grade using the standard Common Terminology Criteria for Adverse Events 5.0 grading system. Based on that grading, treatment should be designed using standard guidelines developed by oncology societies, including the Society for Immunotherapy of Cancer and American Society of Clinical Oncology (ASCO). Most of the toxicities caused by immunotherapy drugs are reversible by using steroid or other immunosuppressive therapies.

It is critical to ensure clinicians recognize and know how to manage these treatment-emergent AEs so patients can seek appropriate medical attention quickly and continue to take advantage of the benefits of immunotherapy.

Several immunotherapy drugs have been approved by the FDA to treat various types of advanced cancers. Approved immunotherapies include CTLA-4 inhibitor ipilimumab (Yervoy); PD-1 inhibitors pembrolizumab (Keytruda), nivolumab (Opdivo), and cemiplimab (Libtayo); and PD-L1 inhibitors atezolizumab (Tecentriq) and avelumab (Bavencio) (TABLE 1).

Immunotherapy AEs can be difficult to identify because they can cause symptoms that are associated with common ailments and infections. Some of these adverse reactions might resemble another medical issue but require a very different course of action. For example, pneumonitis, which a small number of patients on checkpoint inhibitor immunotherapy may experience, can cause some of the same symptoms as viral or bacterial respiratory infection but should be treated with steroids instead of antibiotics. The primary immunotherapy-related AEs patients and clinicians should be aware of include flu-like symptoms, asthenia, arthralgias, and rash. Endocrinopathies such as thyroiditis, hypophysitis, adrenal insufficiency, and type I diabetes must be recognized quickly, as these complications may lead to the need for lifelong hormonal replacement therapy.

There have been reports of inflammation of organs, including pneumonitis, pancreatitis, hepatitis, nephritis, colitis, dermatitis (redness, itchiness, or rash), neuritis, uveitis, and myocarditis. Although myocarditis occurs in fewer than 1% of patients receiving immunotherapy, it is likely the most serious adverse reaction that can occur because of these agents.7 Early detection of this potentially fatal AE, which carries a 40% to 50% risk of death, is critical, but there are currently no clear ways to accurately predict or identify this type of immunotherapy-associated toxicity.

I was recently part of a multidisciplinary team at Roswell Park Comprehensive Cancer Center (Roswell Park) that identified troponin, a protein that enters the bloodstream only when the heart is damaged, as an early and reliable predictor of myocarditis in patients with cancer receiving immunotherapy with immune checkpoint inhibitors.7

Findings of this retrospective study, which reviewed the records of 1001 patients with cancer who were treated with 1 or more immunotherapy agents at Roswell Park from 2016 to 2020, suggested that weekly troponin monitoring during the first 6 weeks of treatment could help physicians detect this rare but potentially fatal AE of immunotherapy. Any patient showing an elevation in troponin levels or signs of cardiotoxicity, such as angina or arrhythmia, should be referred to a cardio-oncology team for complete evaluation, including electrocardiogram, echocardiogram, or cardiac MRI.

Although immunotherapy-related myocarditis is extremely rare, it occurs with greater frequency and severity when immunotherapy drugs are given in combination, and early recognition is critical. For example, in a multicenter analysis, my colleagues and I identified 2 cases of myocarditis that developed in patients with metastatic melanoma following treatment with a combination of ipilimumab and nivolumab, which are 2 commonly used immune checkpoint inhibitors.

Reduction of immunotherapy-related AEs relies heavily on corticosteroids and other immunomodulatory agents, which should be prescribed to reduce the potential for short-term and long-term complications. It remains unclear whether prophylactic antibiotics should routinely be prescribed to reduce the potential for opportunistic infection in patients receiving steroids. Treatment should be individualized depending on each patient’s medical history, comorbidities, and underlying disease status, as well as the type, number, and severity of AEs.

Because immunotherapy is a relatively new treatment option, many of these agents have AEs that have not been previously observed. AEs stemming from immunotherapy use can affect the skin, lungs, gastrointestinal and endocrine systems, joints, heart, and other organs. Some of these AEs are just beginning to be described, therefore clinicians need guidance on how to recognize early signs, how to treat AEs, and when to refer a patient to a disease specialist.

For this reason, I have been helping to create guidance for medical professionals who care for patients receiving immunotherapy drugs. Along with other experts in this field, I helped write the first consensus guidelines on how to recognize and respond to immunotherapy-related AEs and am contributing to similar resources to be issued by ASCO and the National Comprehensive Cancer Network (TABLE 2).

Information is key in identifying and managing any AEs of immunotherapy. It is critical for medical professionals to give patients clear written guidance before a course of immunotherapy is started and to keep that flow of information going back and forth during clinic visits and between appointments.

When my patients on immunotherapy ask me about possible AEs, I stress that immunotherapy is an incredibly important and effective option for treating many cancers and that AEs are rare. I also strongly encourage my patients to become active participants in their treatment by learning about these possible AEs, monitor for these adverse reactions, and respond to any symptoms that develop. Together, we can help to ensure these new and advanced treatments are as effective as possible.

Yervoy. Prescribing information. Bristol Myers Squibb; 2022. Accessed April 7, 2022. 

Keytruda. Prescribing information. Merck Sharp & Dohme Corp; 2022. Accessed April 7, 2022. 

Opdivo. Prescribing information. Bristol Myers Squibb; 2022. Accessed April 7, 2022. 

Libtayo. Prescribing information. Regeneron Pharmaceuticals Inc; 2021. Accessed April 7, 2022. 

Tecentriq. Prescribing information. Genentech; 2022. Accessed April 7, 2022. 

Bavencio. Prescribing information. EMD Sereno, Inc; 2019. Accessed April 7, 2022. 

Puzanov I, Subramanian P, Yatsynovich YV, et al. Clinical characteristics, time course, treatment and outcomes of patients with immune checkpoint inhibitor-associated myocarditis. 

. 2021;9(6):e002553. doi:10.1136/jitc-2021-002553

Tawbi HA, Forsyth PA, Algazi A, et al. Combined nivolumab and ipilimumab in melanoma metastatic to the brain. 

. 2018;379(8):722-730. doi:10.1056/NEJMoa1805453

Puzanov I, Diab A, Abdallah K, et al; Society for Immunotherapy of Cancer Toxicity Management Working Group. Managing toxicities associated with immune checkpoint inhibitors: consensus recommendations from the Society for Immunotherapy of Cancer (SITC) Toxicity Management Working Group. 

. 2017;5(1):95. doi:10.1186/s40425-017-0300-z

Articles

Tackling the Adverse Events of Immunotherapy

Positive survival outcomes among patients with treatment-naive extensive-stage small cell lung (ES-SCLC) cancer were observed after approximately 3.5 years of follow-up following treatment with pembrolizumab (Keytruda) and etoposide, according to data from the phase 3 KEYNOTE-604 trial (NCT03066778) presented at the 

The 36-month overall survival (OS) rate in the pembrolizumab arm was 15.5% compared with 5.9% (HR, 0.76; 95% CI, 0.63-0.93) in the placebo arm, reducing the risk for death by 24%. Moreover, median OS was 10.8 months (95% CI, 9.2-12.9) with pembrolizumab compared with 9.7 months (95% CI, 8.6-10.7) with placebo.

Additionally, the 36-month progression-free survival (PFS) rate was 6.9% in the pembrolizumab arm vs 0.5% in the placebo arm (HR, 0.70; 95% CI, 0.57-0.85). The median PFS was 4.8 months (95% CI, 4.3-5.4) with pembrolizumab compared with 4.3 months (95% CI, 4.2-4.5) with placebo.

“[With 3.5] years of follow-up now, the patients who are on pembrolizumab continue to show clinically meaningful improvements, in particular PFS as well as OS,” Charles Rudin, MD, PhD, chief of thoracic oncology service, codirector of Druckenmiller Center for Lung Cancer Research, and Sylvia Hassenfeld Chair in Lung Cancer Research at Memorial Sloan Kettering Cancer Center, said during a presentation on the findings. “There’s [approximately] a tripling of the 3-year OS rate, [and] about a 20-fold improvement in 2-year PFS. Those patients who have completed [the] full 2 years of pembrolizumab and have durable responses, with the majority, remaining alive now with [approximately] 4 years of follow up after randomization. We need to continue to explore the benefits of immunotherapy in this patient population and see if we can build the tail of the curve to raise it up to 5 or more [years of survival].”

The study included patients with stage IV SCLC who had not previously been treated with a systemic therapy and had an ECOG performance status of 0 or 1. Patients needed to also have a sample available for biomarker analysis. Those who enrolled could not have unstable brain metastases and were required to have adequate organ function and a life expectancy of 3 months or more. Stratification factors included type of cisplatin agent, ECOG performance status, and lactate dehydrogenase level.

A total of 453 patients were randomly assigned 1:1 to receive pembrolizumab at 200 mg on day 1, plus 100 mg/m2 of etoposide on days 1 to 3, and carboplatin or 75 mg/m2 of cisplatin every 3 weeks for 4 cycles (n = 228); or the chemotherapy backbone plus placebo (n = 225). Those in the placebo arm went on to receive maintenance pembrolizumab on day 1 every 3 weeks for up to 31 cycles.

The dual primary end points were progression-free survival (PFS) and OS, with key secondary end points including overall response rate (ORR), duration of response (DOR), and safety.

In the experimental arm, a total of 18 patients completed 35 cycles of treatment with pembrolizumab and 122 went on to receive a subsequent therapy. Fifteen patients received treatment with a subsequent immune checkpoint inhibitor. In the placebo group, 2 patients completed treatment and 220 discontinued due to progressive disease (n = 196), adverse events (AEs; n = 13), consent withdrawal (n = 7), physician decision (n = 3), and protocol violation (n = 1). The median time from randomization to cutoff was 43.3 months.

The median age in the pembrolizumab group was 64.0 years vs 65.0 years in the placebo group, and the majority of patients in both arms were men. Most patients in both the pembrolizumab and placebo cohorts had an ECOG performance status of 1 (73.7% vs 75.1%, respectively) and were current or former smokers (96.5% vs 96.4%). Additionally, 70.6% and 69.3% of patients in both respective cohorts had received treatment with carboplatin.

The overall response rate in the pembrolizumab arm was 70.6% (95% CI, 64.2%-76.4%) vs 61.8% (95% CI, 55.1%-68.2%) in the placebo cohort. Among those in the experimental arm, 2.2% experienced a complete response (CR), 68.4% achieved a partial response, 17.5% had stable disease, and 3.5% had progressive disease. Additionally, the DOR rates at 12, 24, 36, and 42 months or more were 20.7%, 14.6%, 11.5%, and 10.1%, respectively. In the placebo arm, the CR rate was 0.9%, the PR rate was 60.9%, the stable disease rate was 24.9%, and the progressive disease rate was 5.3% The DOR rates at 12, 24, 36, and 42 months or more were 3.3%, 0.8%, 0.8%, and 0.8%, respectively.

All patients in the pembrolizumab arm experienced any-grade of AE and 78.9% experienced grade 3 to 5 AEs. Additionally, 15.7% of patients had AEs that led to discontinuation of any treatment, 4.0% had AEs that led to discontinuation of all treatment, and 6.3% had AEs that led to death. Immune-mediated AEs occurred in 27.4% of patients within this group, 8.1% of which were grade 3 to 5. Additionally, 0.4% of patients in this cohort had grade 3/4 infusion reactions.

In the placebo cohort, 99.6% of patients had any-grade AEs and 77.1% had grade 3 to 5 AEs. In this population, 6.3% of patients had AEs that led to discontinuation of any treatment, 3.6% had AEs that led to discontinuation of all treatments, and 5.4% had AEs that led to death. Immune-mediated AEs were reported in 12.1% of patients, 1.3% of which were grade 3 to 5.

Previous findings from the study indicated that the 12- and 24-month OS rates for patients in the pembrolizumab arm were 45.1% and 23.0%, respectively, compared with 39.6% and 12.7% in the placebo arm. The PFS rate at 12 months and 24 months in the pembrolizumab arm was 17.1% and 11.1%, respectively, vs 5.0% and 0.5% in the placebo arm.

Rudin CM, Kim HR, Navarro A, et al. First-line pembrolizumab or placebo combined with etoposide and platinum for ES-SCLC: KEYNOTE-604 long-term follow-up results. Presented at the 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria. Abstract 1849.

Patients with treatment-naive extensive-stage small cell lung cancer showed encouraging clinical responses with pembrolizumab and etoposide after multiple years of follow-up.

3.5-Year Follow-Up Finds Pembrolizumab/Etoposide Combo Still Effective in Untreated ES-SCLC

The growing availability of biomarkers has led to the advent of more targeted therapies such as the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki (Enhertu), ado-trastuzumab emtansine (Kadcyla; T-DM1), and sacituzumab govitecan-hziy (Trodelvy). As treatments evolve, so too has the nurses’ role in understanding the nuances of sequencing and the safety and efficacy signals of each agent.

“Nurses spend a lot of time with patients and discuss what the oncologist has explained. Understanding the role of biomarkers and how that information is needed so we can make the best recommendation [is important],” Kimberly Podsada, MSN, NP-C, said. “[It is also important to] keep an open line of communication with the oncologist as well, as far as what other markers we might be testing for and staying up to date about these markers because it is a growing field. There have been a stream of new therapies and that has been exciting for us especially over the last few years in breast oncology.”



®, Podsada, a nurse practitioner at University of California San Diego Health in California, discussed the significance of using ADCs in an earlier line of therapy. She also highlighted how advances with oral selective estrogen receptor degraders (SERDs) are giving patients more options and how the integration of new agents is changing the treatment landscape.

How has the role of biomarker testing influenced emerging treatment considerations for patients with breast cancer?

Biomarkers have [become] more available and there are plenty of targeted therapies now because of these additional biomarkers. We are looking at biomarkers that go beyond the estrogen receptor, the progesterone receptor, and the HER2 receptor. Nowadays, we’re also looking at PD-1, PD-L1, the 

 positivity. There are many more markers now that help us to decide [on] treatments for women [in the] adjuvant and metastatic settings.

What are some agents that could challenge existing standards of care or be integrated into the treatment landscape?

In my lifetime in oncology, I have seen a couple of therapies come around that have really changed the treatment landscape, especially for HER2-positive disease. I was a part of the T-DM1 clinical trials when that came to market for the metastatic setting.

Now being a part of the DESTINY-Breast trials, the thing that has really changed the treatment landscape is the DESTINY-Breast03 [NCT03529110] information where trastuzumab deruxtecanhas now bumped T-DM1 for second line. This changes the treatment landscape, especially [in terms of] the median progression-free survival [PFS]. [The median PFS] has not been reached yet.

I am excited to see what happens now when people start using it in the second line of therapy in the metastatic setting.

We also have tucatinib [Tukysa], which is a tyrosine kinase inhibitor [TKI], for metastatic HER2-positive disease. That was an exciting clinical trial [HER2CLIMB trial (NCT02614794)] because it was the first trial that looked at patients with active brain metastases. Usually in a clinical trial, you can see stable brain metastases, but they allowed [individuals] on trial who had new, progressing, and active brain metastases. The TKI displayed a benefit in preventing new lesions from occurring and affecting what we are imagining.

How has the recent influx of approved therapies for patients with HER2-positive metastatic disease affected your practice and how are you addressing sequencing questions?

The sequencing question is always going to be out there. I look at it as we have a lot of tremendous options now for women with HER2-positive disease; T-DM1 in the adjuvant setting, trastuzumab deruxtecan in an earlier line setting for metastatic breast cancer patients, and tucatinib.

Some of it for me is based on conversations with the patient. What are their symptoms? What do they desire, as far as maybe a more oral driven therapy vs an infusion therapy? [Because of] some of the recent approvals, the sequencing will change again with trastuzumab deruxtecan now being able to be used earlier.

As far as what we now do after a second line, I [would say] move on to something like tucatinib as the following therapy, follow guidelines, and figure out the plan in collaboration with your patient because they are the one that is showing up and doing the hard work.

Can you speak to advances with novel medications, such as oral SERDs, for patients with ESR1 mutations?

This is going to be great for patients. Currently, we have an intramuscular injection, fulvestrant [Faslodex], and being able to take something by mouth instead of getting these very large injections will make patients very happy. We are seeing some promising research studies and, although it is still in clinical trials, this is another game changer.

There are always mixed thoughts about someone coming into the clinic or doing their treatment at home. [If they come into the clinic] we know they take their injections and their medicine. At the same time, that causes anxiety and stress because when [an individual] gets injections, they get anxious, and their blood pressure goes up.

If we had an oral version of it, many of us would start with the oral therapy first and I believe we are going to be seeing a couple of new oral SERDs coming to market which will be exciting and give us more options.

How are ADCs reshaping the treatment landscape for patients with TNBC?

ADCs are changing the treatment landscape for all breast cancer types. Trastuzumab deruxtecan and T-DM1, have had some of the biggest positive impacts on the breast cancer world.

In the triple-negative world, which is still an area that I want to see more research go into, it is the most challenging type of breast cancer to treat. We are continuing to come up with new methods of treating it including with ADCs.

Sacituzumab govitecan, has been approved and that is tremendous news for patients and providers to have another option for triple-negative disease. I would like to see some [approved agents] moved up into an earlier line setting—we will have to continue doing clinical trials for that.

There are [AEs] with these medications and a lot of times when some of these drugs are getting approved, they are given to people that have already been heavily pretreated. We are giving these women everything possible.

I’m also curious about what will happen to sequencing over time in the triple negative [space] when [we can start to use] any of these [agents] that are showing great efficacy and potency in an earlier line setting.We are getting there [and] we are making strides to get new therapies out there for triple-negative disease.

We are just trying to give a lot of these patients [better] quality of life as well as [improved] OS. I want women to live longer with their disease, but I also want it to be tolerable for them.

The growing availability of biomarkers has led to the advent of more targeted therapies such as the antibody-drug conjugates (ADCs) fam-trastuzumab deruxtecan-nxki, ado-trastuzumab emtansine, and sacituzumab govitecan-hziy. 

Podsada Discusses Biomarker Testing and ADC Therapies in Breast Cancer 

Because of the risks associated with handling chemotherapy drugs, safety guidelines surrounding their proper use have existed since 1981.

 The Oncology Nursing Society (ONS) and the National Institute for Occupational Safety & Health (NIOSH) have both recommended oncology nurses receive hazardous drug education, including safe storage, preparation, labeling, transportation, administration, and disposal of hazardous drugs and proper use of personal protective equipment (PPE).

In 2016, the United States Pharmacopeial Convention (USP) updated the General Chapter 

<800> to set standards for the safe handling of hazardous drugs, with implementation of the new standards set scheduled for December 2019. Almost 3 years after 

 <800> became the recommended standard, some hospitals have improved their compliance, but Seth Eisenberg, ASN, RN, OCN, BMTCN, a retired oncology nurse now working as a consultant in Saint George, Utah, believes implementing 

 <800> is still a work in progress for many hospitals.

<800> requires pharmacies to store hazardous drugs in an externally ventilated, negative-pressure room with at least 12 air changes per hour,” Eisenberg said in an interview with 

®. “For pharmacies that were housed in the basement of a hospital, this entail[ed] expensive modifications. In some cases, it was more cost-effective to build a new pharmacy rather than retrofit an old one.”

 <800> compliance entails increasing education about proper handling of hazardous drugs, implementing closed system drug-transfer devices (CSTDs), and using requisite PPE, according to Eisenberg. “One of the biggest changes in 

 <800> is the requirement to use CSTDs when administering drugs,” he said. “Although ONS and NIOSH had recommended these devices, they weren’t required.”

CSTDs can prevent or minimize drug leakage, but Eisenberg said the cost can be prohibitive for some hospitals and clinics. “[Because] some components of CSTDs are meant for single use, it increases the overall cost of the medication,” he said. “The average price of a CSTD ranges from $8-$12 a dose.”

 <800> requires nurses to double-glove and wear chemotherapy gowns, when administering chemotherapy drugs, which is consistent with ONS guidelines.

“NIOSH has provided best practice guidance for more than 2 decades. But 

 <800> is an enforceable standard with far-reaching implications for all facilities that handle hazardous drugs,” Eisenberg says.

Although guidelines for safe handling of hazardous oncology drugs aren’t new, 

 <800> introduced safety standards that could be enforceable on a state level.

AnnMarie Walton, PhD, MPH, RN, OCN, CHES, FAAN

 <800> gave teeth and enforceability to safety practices that already existed,” AnnMarie Walton, PhD, MPH, RN, OCN, CHES, FAAN, assistant professor in the School of Nursing at Duke University in Durham, North Carolina, explained in an interview with 

 <800> is still a work in progress for many oncology units. Some of the oncology units that weren’t already using CSTDs are adopting them now that suppliers are able to meet the demand. Enforceability of the 

 <800> requirement is being decided and regulated at the state level.”

Walton said oncology nurses are in a good position to advocate for safety changes and encourage adoption of 

 <800> if their unit hasn’t already implemented them. In addition, oncology nurses can educate patients and their caregivers on safety measures that should be followed while chemotherapy is administered in the hospital or at home after the patient is discharged.

MiKaela M. Olsen, DNP, MS, APRN-CNS, AOCNS, FAAN, clinical program director for oncology at The Johns Hopkins Hospital in Baltimore, Maryland, works at a hospital that began offering a curbside injection clinic to oncology patients in 2020, during the height of the pandemic. 

MiKaela M. Olsen, DNP, APRN-CNS, MS, AOCNS, FAAN

“We had to find a way to ensure our patients could safely continue receiving chemotherapy while also protecting them from the coronavirus,” Olsen told 

Johns Hopkins initially conceived curbside injection clinics as a precaution during the pandemic. But Olsen said Johns Hopkins plans to continue these clinics for patients receiving chemotherapy, and other hospitals have taken notice. “For many oncology patients, the curbside injection clinic offers both increased safety and convenience,” Olsen said. “They still have the option of our indoor injection clinic, but for patients with transportation and mobility issues, the curbside clinic is easier. They can have a family member drive them or take an Uber or Lyft to their appointment.”

Nurses staffing the curbside injection clinic wear full PPE, follow safety protocols, and offer services including symptom assessment, port flushes, dressing changes, and chemotherapy. To date, the curbside injection clinic has seen over 7000 patients. Although large health systems such as Johns Hopkins have embraced 

<800>, Olsen acknowledged that some smaller community hospitals are still working to implement 

 <800> safety requirements. One way for hospitals to do this is to request a Health Hazard Evaluation from NIOSH. This evaluation identifies potential health hazards and recommends ways to reduce exposure. There is no cost for the evaluations, but they pay off by providing peace of mind.  “Compliance challenges vary from one health care setting to the next, but nurses can help identify areas in need of improvement,” Olsen said. 

Bernabeu-Martínez MA, Ramos Merino M, Santos Gago JM, Álvarez Sabucedo LM, Wanden-Berghe C, Sanz-Valero J. Guidelines for safe handling of hazardous drugs: a systematic review. 

. 2018;13(5):e0197172. doi:10.1371/journal.pone.0197172

USP<800> Compliance: A Hazardous Drug Safe-Handling Quality Improvement Project for Ambulatory Care Infusion Nurses

. Doctor of Nursing Practice thesis. University of San Francisco; 2020.https://repository.usfca.edu/dnp/218

Powerful chemicals used in chemotherapy may pose safety hazards for oncology nurses, pharmacists, and other health care providers if not handled properly.

USP <800>: Still a Work in Progress?

A trend in overall survival (OS) improvement was observed among patients with resected non–small cell lung cancer (NSCLC) who were treated with atezolizumab (Tecentriq) vs best supportive care, according to phase 3 findings from the IMpower010 trial (NCT02486718).

showed that at a median follow-up of 46 months the median OS in patients with PD-L1 expression of at least 1% was not reached in the atezolizumab group (n = 248) or best supportive care group (n = 228; HR, 0.71; 95% CI, 0.49-1.03). Moreover, the OS rates at 36 months and 60 months were 82.1% and 76.8% in the atezolizumab group, respectively, compared with 78.9% and 67.5% in the best supportive care group.

In all patients who were randomized to treatment, the median OS was not reached in the atezolizumab (n = 442) and best supportive care groups (n = 440; HR, 0.95; 95% CI, 0.74-1.24), respectively. OS events occurred in 26.0% and 26.4% of patients in each respective group. In the intent-to-treat (ITT) population, the median OS was also not reached in either the atezolizumab (n = 507) or best supportive care (n = 498) cohorts (HR, 0.995; 95% CI, 0.78-1.28; 

 = .9661). OS events were reported in 25.0% and 24.9% of patients in each group, respectively.

Further, the investigators conducted a subgroup analysis in patients with PD-L1–positive stage II/IIIA disease.

“We performed the subgroup analysis of OS…there is a trend towards an improvement in [OS] for those patients receiving atezolizumab,” according to lead author Enriqueta Felip, MD, PhD, head of the lung cancer unit, Department of Oncology at Vall d’Hebron University Hospital. “We can see that for those patients with squamous cell carcinoma, the hazard ratio for OS was 0.85; for those patients with nonsquamous cell, it was 0.61; for those patients with pathological stage IIA [disease], the HR was 0.75; for [those with] stage IIB [disease, the HR was] 0.64; and [for] stage IIIA [disease], it was 0.70.”

The study included patients with stage IB to IIIA tumors that were 4 cm or greater who had an ECOG performance status of 0 or 1. Patients also needed to have undergone a lobectomy and have tumor tissue available for PD-L1 analysis.

Patients (n = 1280) initially received treatment with cisplatin and pemetrexed, gemcitabine, docetaxel, or vinorelbine for 1 to 4 cycles of treatment and were then randomized 1:1 (n = 1005) to either the experimental or control group. Patients in the experimental group were then treated with 1200 mg of atezolizumab every 21 days for 16 cycles or 1 year, and the placebo group received best supportive care. Patients were stratified based on sex, stage, histology, and PD-L1 status.

The primary end point was investigator-assessed disease-free survival (DFS) tested hierarchically, with secondary end points including OS in the ITT population, DFS in the PD-L1 population, and 3- and 5-year DFS. OS biomarker analyses were also performed as part of an experimental end point.

A previous readout from an interim analysis indicated that at a median follow up of 32.0 months,

 the OS data were not mature, with investigators citing an event-to-patient ratio of 19% in the ITT population and 18% in the best supportive care arm. The hazard ratios (HR) were 0.77 (95% CI, 0.51-1.17) in those with PD-L1 expression of 1% or more, 0.99 (95% CI, 0.73-1.33)

in all randomized patients, and 1.07 (95% CI, 0.80-1.42) in the ITT population.

Moreover, HRs for DFS were 0.66 (95% CI, 0.50-0.88; 

 = .0039) for the PD-L1 expression of 1% or more population, 0.79 (95% CI, 0.64-0.96; P = .0205) in the overall randomized population, and 0.81 (95% CI, 0.67-0.99; P =.0395) in the ITT population.

Additional findings from the study indicated that the OS rates at 36 months and 60 months among those with a PD-L1 expression of 50% of more who were treated with atezolizumab were 89.1% and 84.8%, respectively, vs 77.5% and 67.5% in the best supportive care arm. Median OS was not reached in either arm (HR, 0.42; 95% CI, 0.23-0.78).

Any-grade adverse events (AEs) were reported in 92.5% of patients in the atezolizumab arm and 70.9% in the best supportive care arm, of which 67.9% and 0.0%, respectively, were treatment related. Moreover, 22.0% and 11.5% of AEs in either arm were grade 3/4, 10.7% and 0.0% of which were treatment related. Investigators also reported that 7.5% of patients in the atezolizumab arm and 0.0% of those in the best supportive care arm experienced serious treatment-related AEs, and 1.8% and 0.6% had grade 5 AEs, respectively. Additionally, 28.7% and 18.2% of patients in the atezolizumab arm required a dose interruption or treatment withdrawal due to AEs vs no patients in the control group.

Felip concluded by stating the trial will be continuing to the final DFS and OS analysis.

Felip E, Altorki N, Vallieres E, et al. IMpower010: overall survival interim analysis of a phase III study of atezolizumab vs best supportive care in resected NSCLC. Presented at the 2022 World Conference on Lung Cancer; August 6-9, 2022; Vienna, Austria; PL03.09.

Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB–IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. 2021;398(10308):1344-1357. doi:10.1016/S0140-6736(21)02098-5

Phase 3 findings from the IMpower010 trial show that patients with resected non–small cell lung cancer may achieve an overall survival benefit with atezolizumab. 

Atezolizumab Signals OS Improvement in Patients with Resected NSCLC

Lindsay Fischer is the Associate Editor at ONN. She joined MJH life sciences in 2021 after graduating from Rutgers University with majors in both English and Spanish and a minor in creative writing. When she is not writing, or researching the latest oncology nursing news, Lindsay is an amateur backpacker and rollerblader. Email Lindsay at lfischer@mjhlifesciences.com

Podcasts

Stephanie Jackson, DNP, MSN, RN, AOCNP, BMTCN, discusses the trajectory of targeted and CAR T-cell therapies such as ivosidenib and brexucabtagene autoleucel, and what nurses need to know about these treatments to be able to practice at the top of their licensure.

Stephanie Jackson Unpacks Recent Advances in Leukemia Treatments

Extended follow-up data from 2 trials confirmed that larotrectinib yielded positive progression-free and overall survival outcomes for patients with NTRK-positive lung cancer.

Larotrectinib Holds Ground as Effective Treatment in NTRK-Positive Lung Cancer

Phase 1 findings showed a 50% overall response rate among patients with EGFR-mutated non–small cell lung cancer who received amivantamab in combination with lazertinib plus carboplatin and pemetrexed.

Amivantamab/Lazertinib/Chemo Regimen Gains Traction in EGFR-Mutant NSCLC

Videos

Sherry Adkins, MSN, ANP-C, discusses some key considerations in ensuring quality patient care after they have completed CAR T-cell therapy at a specialized center.

Sherry Adkins Talks Primary Care Provider Communication Following CAR T-cell Therapy

The FDA has approved trastuzumab deruxtecan for patients with HER2-mutated non–small cell lung cancer after the DESTINY-Lung02 results demonstrated a 57% overall response rate with the agent. The drug comes with warning for interstitial lung disease, neutropenia, and left ventricular dysfunction. 

HER2-Directed Therapy, Trastuzumab Deruxtecan, Approved for Metastatic NSCLC

The FDA has granted capmatinib regular approval for patients with metastatic non–small cell lung cancer (NSCLC) whose tumors have a mutation leading to MET exon 14 skipping. The drug comes with warning for pneumonitis, hepatotoxicity, and pancreatic toxicity. 

Capmatinib Snags Full FDA Approval for MET Exon 14 Skipping NSCLC

In an unprecedented age of health care burnout, hospital administrators may
need to think outside of the box to find ways to engage and support employees.

Structured Onboarding Processes Boost Employee Retention 

Avelumab, erdafitinib, and enfortumab vedotin-ejfv are 3 critical drugs in the treatment of urothelial cancer with distinct safety profiles, according to a presentation at the 6th Annual School of Nursing Oncology™ Meeting. 

Approaches to Urothelial Care Call for Nuanced AE Management

A biologics license application for the IL-15 superagonist N-803 has been accepted and the agent will be reviewed for the treatment of patients with Bacillus Calmette-Guérin–unresponsive non–muscle invasive bladder cancer carcinoma in situ.

N-803 BLA Undergoes Review For BCG-Unresponsive Non–Muscle Invasive Bladder Cancer in Situ

In a presentation at the 6th Annual School of Nursing Oncology™, Laura Wood, RN, MSN, OCN, highlights key nurse takeaways with VEGF TKI/immune checkpoint inhibitor therapy for patients with renal cell carcinoma. 

Evolution of Frontline VEGF TKI/Immunotherapy Treatments Propels Field of Renal Cell Carcinoma

At the 6th Annual SONO meeting, Kelley A. Rone, DNP, RN, AGNP-C, reviewed evidence supporting molecular testing in patients with colorectal cancer. 

Molecular Profiling Is a Necessity in Colorectal Cancer Treatment 

Patients with previously treated non–small cell lung cancer experienced a median overall survival of 16.9 months with second- or third-line tislelizumab vs 11.9 months with docetaxel. 

Tislelizumab Maintains Superior Overall Survival Benefit Vs Docetaxel in Pretreated NSCLC

Paula Anastasia, RN, MN, AOCN, highlights circumstances in which patients may not be eligible to receive benefit with a PARP inhibitor. 

Paula Anastasia on PARP Inhibitor Ineligibility Factors for Women With Ovarian Cancer

Treatments options for various histologies of leukemia are expanding with FDA approvals for drugs such as the combination of ivosidenib/azacitidine and the CAR T-cell therapy brexucabtagene autoleucel.

Nurses Adapt to New Hematology Advances and Approvals in Leukemia Treatment  

Patients with hormone-sensitive prostate cancer who received darolutamide in combination with docetaxel experienced superior overall survival and time-to-pain progression benefit. 

Top Medical News

Tackling the Adverse Events of Immunotherapy

3.5-Year Follow-Up Finds Pembrolizumab/Etoposide Combo Still Effective in Untreated ES-SCLC

Podsada Discusses Biomarker Testing and ADC Therapies in Breast Cancer

USP <800>: Still a Work in Progress?

Atezolizumab Signals OS Improvement in Patients with Resected NSCLC

Most Recent