Neoadjuvant nivolumab (Opdivo) plus chemotherapy significantly improved pathologic complete response (pCR) rates versus chemotherapy alone in patients with resectable stage IB-IIIA non–small-cell lung cancer (NSCLC), according to final results from the CheckMate-816 clinical trial. These findings were presented by Patrick Forde, MBBCh, Associate Professor of Oncology and Director of the Thoracic Cancer Clinical Research Program at Johns Hopkins University Sidney Kimmel Comprehensive Cancer Center, Baltimore, MD, during the virtual 2021 American Association for Cancer Research Annual Meeting.
“The standard treatment for resectable lung cancer is surgery to remove the tumor. Despite this, many patients experience recurrence of their lung cancer, and when it happens, it is usually incurable. For the first time in a phase 3 trial, we see the potential for an anti–PD-L1 immunotherapy to improve outcomes in earlier-stage NSCLC,” he said.
In the randomized, phase 3, open-label CheckMate-816 trial, investigators compared neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone in 358 newly diagnosed patients with resectable stage IB to IIIA NSCLC. Patients had no sensitizing EGFR or ALK mutations and were stratified by stage, PD-L1 status, and sex.
Patients were randomized in a 2:1 ratio to nivolumab 360 mg every 3 weeks plus chemotherapy (platinum doublet) every 3 weeks for 3 cycles or the same schedule with chemotherapy alone. Radiologic staging and surgery were performed within 6 weeks of neoadjuvant therapy.
A total of 98% of all patients enrolled in the trial received neoadjuvant therapy; 94% of the nivolumab-containing arm and 84% of the chemotherapy arm completed treatment, and 83.2% and 75.4%, respectively, completed surgery. Lung-sparing surgery (lobectomy) was performed in 77% versus 61%, respectively. The primary end point of the trial was pCR, based on several studies suggesting that achieving pCR on neoadjuvant therapy is associated with improved survival.
Nivolumab plus chemotherapy improved the pCR rate from 2.2% in the chemotherapy arm to 24% according to an intent-to-treat analysis, representing a highly significant 86% improvement favoring the addition of nivolumab (P <.0001), with an absolute difference of 22.8% between the 2 treatment arms.
A subgroup analysis showed that pCR was superior with neoadjuvant nivolumab plus chemotherapy versus chemotherapy alone regardless of histology, PD-L1 status, and tumor mutational burden.
In a subset of available samples, circulating tumor DNA was more likely to clear when nivolumab was added to chemotherapy: 56% versus 34% for chemotherapy alone; the pCR rate was 46% in patients with circulating tumor DNA clearance versus 13% in those without it.
The rates of adverse events were relatively similar in both arms. Grades 3 and 4 adverse events were reported in 33.5% of the nivolumab plus chemotherapy arm versus 36.9% in the chemotherapy-alone arm. Grade 5 surgery-related adverse events occurred in 2 patients in the combination arm and were deemed unrelated to the study drugs.
Dr Forde stated that the high pCR rates plus the favorable toxicity profile and the fact that the neoadjuvant therapy did not decrease the chances of surgery suggest that neoadjuvant nivolumab plus chemotherapy is a viable option for patients with NSCLC at high risk for recurrence.
“We are highly encouraged by the marked improvement in pCR, the good overall tolerability, and the absence of impact on feasibility of surgery when nivolumab is added to neoadjuvant chemotherapy,” Dr Forde said. “While neoadjuvant chemotherapy has historically been less commonly used than adjuvant chemotherapy for this patient population, I believe that CheckMate-816 has the potential to change that treatment paradigm,” he added.