The integration of chemoimmunotherapy regimens with checkpoint inhibitors is transforming the treatment landscape for resectable non-small cell lung cancer (NSCLC). Recent studies and clinical trials highlight the effectiveness of these combination therapies in improving patient outcomes. Data suggest that neoadjuvant immune checkpoint inhibitors (ICIs) combined with chemotherapy, followed by adjuvant ICI therapy, are becoming a standard of care for eligible patients.
Durvalumab's Impact on Resectable NSCLC
The FDA's August 15, 2024, approval of neoadjuvant durvalumab (Imfinzi) plus platinum-based chemotherapy, followed by adjuvant durvalumab monotherapy, marks a significant advancement. This regimen is indicated for adult patients with resectable NSCLC who do not have ALK or EGFR alterations. The phase 3 AEGEAN trial (NCT03800134) demonstrated that this treatment reduced the risk of disease progression, recurrence, or death by 32% compared to neoadjuvant platinum-based chemotherapy plus placebo followed by adjuvant placebo. The median event-free survival (EFS) was not reached in the durvalumab arm versus 25.9 months in the placebo arm (HR, 0.68; 95% CI, 0.53-0.88; P = .0039). The pathologic complete response (pCR) rate was also significantly higher at 17.2% compared to 4.3% in the placebo group (P < .0001).
Nivolumab's Role in Improving Outcomes
Findings from the phase 3 CheckMate 77T study (NCT04025879) further support the use of checkpoint inhibitors in combination with chemotherapy. The study showed that adding nivolumab (Opdivo) to chemotherapy significantly extended EFS compared to chemotherapy alone (HR, 0.58; 97.36% CI, 0.42-0.81; P < .001). The pCR rate also improved, with 25.3% in the nivolumab arm versus 4.7% in the chemotherapy arm (OR, 6.64; 95% CI, 3.40-12.97).
Pembrolizumab's Effect on Overall Survival
The phase 3 KEYNOTE-671 trial (NCT03425643) led to the FDA approval of neoadjuvant pembrolizumab (Keytruda) plus platinum-containing chemotherapy, followed by single-agent adjuvant pembrolizumab, for patients with resectable NSCLC. At a median follow-up of 29.8 months, the pembrolizumab regimen significantly improved overall survival (OS) compared to placebo plus chemotherapy followed by adjuvant placebo, reducing the risk of death by 28% (HR, 0.72; 95% CI, 0.56-0.93; 1-sided P = .00517).
Managing Treatment-Related Adverse Events
While chemoimmunotherapy regimens show promise, it's crucial to consider treatment-related adverse events (TRAEs). In CheckMate 77T, TRAEs occurred in 89.0% of patients receiving the nivolumab regimen and 87.0% of those receiving chemotherapy/placebo. These events led to treatment discontinuation in 19.3% versus 7.4% of patients, respectively. In AEGEAN, serious AEs occurred in 37.7% of patients receiving the durvalumab regimen compared with 31.4% of patients receiving the chemotherapy/placebo regimen, leading to discontinuation in 12.0% vs 6.0% of patients, respectively.
Addressing Oligoprogression
Experts are also considering new treatment strategies for patients experiencing oligoprogression. The concept involves using local, targeted therapies, such as checkpoint inhibition, for persisting disease sites in both small cell lung cancer and NSCLC, even in the face of progression. This approach aims to regain disease control in patients who initially responded well to systemic therapy.
Expert Perspectives
Mark G. Kris, MD, a thoracic medical oncologist at Memorial Sloan Kettering Cancer Center, emphasized the significant impact of perioperative checkpoint inhibitors, stating, "I urge physicians to give patients with early-stage lung cancers who are candidates for surgery checkpoint inhibitors plus chemotherapy whenever possible... You have the best chance to make a huge impact in patients’ lives with that approach."
