Dr Kazmi Discusses the CheckMate 77T Trial in Resectable Stage III NSCLC
Presenter
Shayma Kazmi, MD, University of Pennsylvania
Conference
2024 ASCO Direct™ Philadelphia
The Bottom Line
CheckMate 77T evaluated the addition of perioperative nivolumab (an immune checkpoint inhibitor) with chemotherapy in patients with stage III resectable non-small cell lung cancer (NSCLC), with a focus on those with N2 disease (advanced lymph node involvement). Results showed that nivolumab combined with chemotherapy improved event-free survival (EFS) and surgical downstaging (reduction in cancer severity before surgery) in patients with both single-station and multi-station N2 disease. Dr. Shayma Kazmi highlighted that these findings could shift perceptions around the treatability of patients with N2 disease in NSCLC, potentially allowing more patients access to curative intent surgery.
Background
Treatment for stage III non-small cell lung cancer (NSCLC) with lymph node involvement (N2) disease is typically a more challenging scenario because patients are often considered unresectable due to their more extensive lymph node involvement. Recent advances in the neoadjuvant (pre-surgery) use of immunotherapy, however, may offer a promising approach to help improve surgical outcomes in these patients. In her recent presentation at the 2024 ASCO Direct™ Philadelphia Conference, Dr Shayma Kazmi from University of Pennsylvania highlighted results from the CheckMate 77T trial, which was designed to evaluate if adding nivolumab immunotherapy to standard chemotherapy before surgery could enhance outcomes and improve the feasibility of surgery in this high-risk group of patients.
Trial Design and Patients
CheckMate 77T enrolled patients with resectable stage II to IIIb NSCLC who did not have mutations in EGFR or ALK. The study participants were randomly assigned to receive either nivolumab plus chemotherapy or a placebo with chemotherapy. Nivolumab immunotherapy was chosen on the basis of its ability to enhance immune responses, potentially making tumors more amenable to surgery. All patients received four cycles of therapy before surgery, after which they were re-evaluated, and some patients continued with adjuvant nivolumab therapy.
Main Trial Results
Results from CheckMate 77T presented at this year’s Annual Meeting of the American Society for Clinical Oncology (ASCO) showed a benefit of adding neoadjuvant nivolumab in the following study endpoints:
Event-Free Survival (EFS): Patients who received nivolumab in combination with chemotherapy had a significant improvement in EFS compared to those in the placebo group. At 18 months, approximately 70% of the nivolumab group remained event-free compared to 50% in the placebo group.
Pathologic Complete Response (pCR): Patients on nivolumab achieved a pCR of about 24% in patients with single-station N2 disease and 37% in those with multi-station N2 disease. Dr. Kazmi emphasized that these rates reflect significant tumor shrinkage and downstaging, which are crucial for improving surgical outcomes.
Downstaging and Resectability: Patients treated with nivolumab were more likely to experience downstaging to less advanced nodal involvement (yPN0), with almost half achieving this outcome compared to only one-third achieving the same outcome in the placebo group. This indicates that perioperative nivolumab can improve surgical feasibility in N2 patients, allowing more to undergo potentially curative resection.
Adverse Events and Toxicities
Treatment with nivolumab plus chemotherapy was generally well-tolerated, with immune-mediated adverse events, such as skin rash and diarrhea being most common. The overall rate of adverse events, however, was higher in the nivolumab arm compared to placebo. The safety profile was consistent with other immunotherapies, with most events being grade 1 or 2, indicating that the combination treatment was generally safe for patients with resectable NSCLC.
Conclusions and Faculty Insights
Dr. Kazmi expressed optimism about CheckMate 77T’s impact on the management of resectable stage III NSCLC with N2 disease, noting that the trial provides evidence that neoadjuvant nivolumab can improve outcomes and enable more effective surgical options. She emphasized that these findings support a re-evaluation of surgical options for patients with N2 disease, which has traditionally been considered more challenging to treat. Dr. Kazmi also stressed the importance of multidisciplinary team planning, as treatment of advanced NSCLC often requires close collaboration between medical oncologists and thoracic surgeons to determine the best therapeutic strategy.
Speaker Disclosure Information: Dr. Kazmi did not report any relevant disclosures for this presentation.