clinical topic updates

Adjuvant Immunotherapy in Non–Small Cell Lung Cancer

by Jeffrey Crawford, MD

Overview

Immunotherapy with immune checkpoint inhibitors (ICIs) has revolutionized the treatment of late-stage non–small cell lung cancer (NSCLC). Emerging evidence suggests that these agents might also have a similar potential in the adjuvant setting, in earlier stages of the disease; however, further investigation is needed.

Expert Commentary

Jeffrey Crawford, MD

George Barth Geller Professor for Research in Cancer
Duke University Medical Center
Lead PI of NCTN LAPS Grant
Duke Cancer Institute
Durham, NC

“We are optimistic about data emerging from ICI trials in conjunction with surgery, and we hope that FDA-approved options will be available in the future." 

Jeffrey Crawford, MD

The introduction of ICI therapy has led to dramatic improvements in outcomes in patients with advanced NSCLC, with many individuals achieving durable benefits. We are hopeful that the addition of ICI therapy will also increase the cure rate in patients with earlier-stage disease. There is evidence that platinum-based chemotherapy increases the cure rate in the induction setting, preoperatively, and in the adjuvant setting, postoperatively. More recently, the anti-EGFR agent osimertinib became the first targeted therapy to be approved by the US Food and Drug Administration (FDA) in the adjuvant setting for patients with NSCLC with EGFR exon 19 deletions or EGFR exon 21 L858R mutations.

Whether the advances that we are observing with ICIs in advanced-stage disease will also translate to the adjuvant or neoadjuvant setting is the subject of a number of ongoing trials, and results are beginning to emerge. At the 2021 American Society of Clinical Oncology Annual Meeting, the interim results of the phase 3 IMpower010 study were reported. Adjuvant atezolizumab was administered after chemotherapy in patients with stage II to IIIA NSCLC. The interim results showed a statistically significant improvement in disease-free survival compared with best supportive care. The magnitude of disease-free survival benefit was particularly pronounced in the PD-L1–positive population.

Other ongoing adjuvant trials include those assessing nivolumab (the ANVIL trial; NCT02595944), pembrolizumab (the PEARLS trial; NCT02504372), and durvalumab (NCT02273375).

In the neoadjuvant setting, results from the CheckMate-816 trial recently presented at the American Association for Cancer Research Annual Meeting 2021 indicated that the addition of nivolumab to chemotherapy in patients with stage IB to IIIA resectable NSCLC prior to surgery was associated with an increased pathological complete response rate compared with chemotherapy alone (24% vs 2.2%).

All of this is new territory, so we will need to watch and learn from what emerges. There are several unanswered questions. Will the ICI therapies vary in terms of benefit? How long should we use ICI treatment? And I would say that one of the most important questions is: Should we prescribe ICI therapy preoperatively, postoperatively, or both?

For now, patients need to know that they may have the opportunity to participate in pre- or postoperative ICI therapy studies, and that is part of the overall discussion of treatment for NSCLC. Thus, we are optimistic about data emerging from ICI trials in conjunction with surgery, and we hope that FDA-approved options will be available in the future.

References

ClinicalTrials.gov. Double blind placebo controlled study of adjuvant MEDI4736 in completely resected NSCLC. Accessed July 15, 2021. https://clinicaltrials.gov/ct2/show/NCT02273375

ClinicalTrials.gov. Nivolumab after surgery and chemotherapy in treating patients with stage IB-IIIA non-small cell lung cancer (an ALCHEMIST treatment trial) (ANVIL). Accessed July 15, 2021. https://www.clinicaltrials.gov/ct2/show/NCT02595944

ClinicalTrials.gov. Study of pembrolizumab (MK-3475) vs placebo for participants with non-small cell lung cancer after resection with or without standard adjuvant therapy (MK-3475-091/KEYNOTE-091) (PEARLS). Accessed July 15, 2021. https://www.clinicaltrials.gov/ct2/show/NCT02504372

Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage 1B-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. J Clin Oncol. 2020;38(suppl 18):LBA5. doi:10.1200/JCO.2020.38.18_suppl.LBA5

Neoadjuvant nivolumab plus chemotherapy increased pathological complete response rate in CheckMate-816 lung cancer trial. News release. American Association for Cancer Research. April 10, 2021. Accessed July 15, 2021. https://www.aacr.org/about-the-aacr/newsroom/news-releases/neoadjuvant-nivolumab-plus-chemotherapy-increased-pathological-complete-response-rate-in-checkmate-816-lung-cancer-trial/

Non-small Cell Lung Cancer Collaborative Group. Chemotherapy in non-small cell lung cancer: a meta-analysis using updated data on individual patients from 51 randomised clinical trials. BMJ. 1995;311(7010):899-909.

Owen D, Chaft JE. Immunotherapy in surgically resectable non-small cell lung cancer. J Thorac Dis. 2018;10(suppl 3):S404-S411. doi:10.21037/jtd.2017.12.93

Pivotal phase III study shows Roche’s Tecentriq helped people with early lung cancer live longer without their disease returning. News release. Roche Group Media Relations. March 22, 2021. Accessed July 15, 2021. https://www.roche.com/media/releases/med-cor-2021-03-22.htm 

Vansteenkiste JF, Cho BC, Vanakesa T, et al. Efficacy of the MAGE-A3 cancer immunotherapeutic as adjuvant therapy in patients with resected MAGE-A3-positive non-small-cell lung cancer (MAGRIT): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2016;17(6):822-835. doi:10.1016/S1470-2045(16)00099-1

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

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