Perioperative nivolumab improves outcomes in resectable NSCLC
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Key takeaways:
- Individuals with resectable NSCLC had improved EFS if they received perioperative nivolumab in addition to standard of care therapy.
- Perioperative nivolumab had a similar safety profile as standard of care.
Immunotherapy before and after surgery significantly improved EFS compared with neoadjuvant immunotherapy only for patients with resectable non-small cell lung cancer, according to a comparison of results from two randomized phase 3 trials.
The benefit with perioperative immunotherapy persisted regardless of patients’ cancer stage disease stage at baseline, findings presented at International Association for the Study of Lung Cancer (IASLC) World Conference on Lung Cancer showed.
“There’s been a big migration in lung cancer and in melanoma treatment in the last few years from doing surgery upfront and giving postoperative immunotherapy, to giving immunotherapy prior to surgery,” Patrick M. Forde, MBBCH, adjunct professor of oncology, co-director of the division of upper aerodigestive malignancies and director of the thoracic oncology clinical research program at Johns Hopkins University School of Medicine, said in a press release. “But our analysis in individual patients in these two trials suggests that there is likely a further benefit from receiving additional immunotherapy treatment after surgery.”
Background and methods
Nivolumab (Opdivo, Bristol Myers Squibb) is an anti-PD-1 antibody.
Neoadjuvant nivolumab plus chemotherapy has become the standard of care for individuals with resectable NSCLC based on results of the CheckMate 816 trial, which showed improved EFS and pathologic complete response (pCR) with the combination vs. chemotherapy alone, according to study background.
The CheckMate 77T trial showed patients who received perioperative nivolumab — administered with chemotherapy in the neoadjuvant setting and as monotherapy in the adjuvant setting — achieved longer EFS and were more likely to achieve pCR compared with those who only received neoadjuvant chemotherapy.
Forde and colleagues conducted a comparative analysis of both trials to determine which patients could benefit from perioperative nivolumab.
One group included 139 individuals (48% aged younger than 65 years; 73% men; 27% Asian) from the CheckMate 77T trial who received up to four cycles of neoadjuvant nivolumab plus chemotherapy, followed by at least one dose of adjuvant nivolumab.
The other group included 147 individuals (52% aged younger than 65 years; 69% men; 50% Asian) from the CheckMate 816 trial who received three cycles of neoadjuvant nivolumab plus chemotherapy, followed by surgery.
Median follow-up was 33.3 months for the CheckMate 77T cohort and 29.5 months for the CheckMate 816 cohort.
EFS from surgery (weighted and unweighted) and in subgroups (unweighted) based on PD-L1 expression, cancer stage and pCR status served as the key outcome measure. Researchers also assessed safety.
Results and next steps
Results showed patients who received perioperative nivolumab achieved longer EFS, with both weighted analyses and one unweighted analysis suggesting about a 40% improvement.
One weighted analysis designed to show stabilized average treatment effect showed a 39% improvement in EFS with perioperative nivolumab (HR = 0.61; 95% CI, 0.39-0.97).
Subgroup analyses showed perioperative nivolumab conferred similar EFS benefit regardless of disease stage (stage IB/stage II, HR = 0.53; 95% CI, 0.25-1.11; stage III, HR = 0.63; 95% CI, 0.37-1.07) or pCR status (pCR, HR = 0.58; 95% CI, 0.14-2.4; no pCR, HR = 0.65; 95% CI, 0.4-1.06).
Results showed greater EFS benefit among patients with PD-L1 expression on less than 1% of tumor cells (HR = 0.51; 95% CI, 0.28-0.93) than those with PD-L1 expression of 1% or greater (HR = 0.86; 95% CI, 0.44-1.7).
Regarding grade 3 to grade 4 adverse events, the perioperative group had lower rates of treatment-related adverse events (27% vs. 35%), but higher rates of treatment-related adverse events that led to discontinuation (6% vs. 5%) and serious adverse events (27% vs. 11%).
A higher percentage of patients who received perioperative nivolumab experienced any-grade treatment-related adverse events (94% vs. 85%); however, grade 3/grade 4 treatment-related adverse events occurred more frequently among patients who only received nivolumab in the neoadjuvant setting (35% vs. 27%).
Rates of grade 3/grade 4 treatment-related adverse events leading to discontinuation (6% vs. 5%) and treatment-related serious adverse events (10% vs. 9%) were comparable between the perioperative and neoadjuvant-only groups. No treatment-related deaths occurred.
“These results should be interpreted with caution given the exploratory nature of the analysis,” researcher Tina Cascone, MD, PhD, associate professor at The University of Texas MD Anderson Cancer Center, said in a press release. “Nevertheless, the findings are very encouraging and provide a foundation for thoughtful discussions with our patients regarding treatment options for their disease.”
References:
- Forde PM, et al. Abstract 3589. Presented at: IASLC World Conference on Lung Cancer; Sept. 7-10, 2024; San Diego.
- Immunotherapy before and after lung cancer reduces death risk and disease recurrence, research finds (press release). Available at: https://medicalxpress.com/news/2024-09-immunotherapy-lung-cancer-surgery-death.html. Published Sept. 8. 2024. Accessed Sept. 8. 2024.
- Perioperative nivolumab may provide meaningful improvement in event-free survival compared to only neoadjuvant nivolumab plus chemotherapy for resectable NSCLC (press release). Available at: https://www.prweb.com/releases/perioperative-nivolumab-may-provide-meaningful-improvement-in-event-free-survival-compared-to-only-neoadjuvant-nivolumab-plus-chemotherapy-for-resectable-nsclc-302241247.html. Published Sept. 8. 2024. Accessed Sept. 8. 2024.
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Forde PM, et al. Abstract 3589. Presented at: IASLC World Conference on Lung Cancer; Sept. 7-10, 2024; San Diego.
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