Neoadjuvant nivolumab plus chemotherapy in resectable non-small-cell lung cancer in Japanese patients from CheckMate 816

Abstract

In the open-label, phase III CheckMate 816 study (NCT02998528), neoadjuvant nivolumab plus chemotherapy demonstrated statistically significant improvements in event-free survival (EFS) and pathological complete response (pCR) versus chemotherapy alone in patients with resectable non-small-cell lung cancer (NSCLC). Here we report efficacy and safety outcomes in the Japanese subpopulation. Patients with stage IB-IIIA, resectable NSCLC were randomized 1:1 to nivolumab plus chemotherapy or chemotherapy alone for three cycles before undergoing definitive surgery within 6 weeks of completing neoadjuvant treatment. The primary end-points (EFS and pCR) and safety were assessed in patients enrolled at 16 centers in Japan. Of the Japanese patients randomized, 93.9% (31/33) in the nivolumab plus chemotherapy arm and 82.9% (29/35) in the chemotherapy arm underwent surgery. At 21.5 months' minimum follow-up, median EFS was 30.6 months (95% confidence interval [CI], 16.8-not reached [NR]) with nivolumab plus chemotherapy versus 19.6 months (95% CI, 8.5-NR) with chemotherapy; hazard ratio, 0.60 (95% CI, 0.30-1.24). The pCR rate was 30.3% (95% CI, 15.6-48.7) versus 5.7% (95% CI, 0.7-19.2), respectively; odds ratio, 7.17 (95% CI, 1.44-35.85). Grade 3/4 treatment-related adverse events were reported in 59.4% versus 42.9% of patients, respectively, with no new safety signals identified. Neoadjuvant nivolumab plus chemotherapy resulted in longer EFS and a higher pCR rate versus chemotherapy alone in Japanese patients, consistent with findings in the global population. These data support nivolumab plus chemotherapy as a neoadjuvant treatment option in Japanese patients with resectable NSCLC.

Keywords: Japanese; minimally invasive surgical procedure; neoadjuvant therapy; nivolumab; non-small-cell lung carcinoma.

FIGURE 1

Treatment disposition in Japanese patients with resectable non‐small‐cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy or chemotherapy alone. Database lock: October 20, 2021; minimum follow‐up, 21.5 months; median follow‐up, 29.7 months. ^aScreen failure. ^bIncludes the following patients: (i) 113 patients who were randomized to an exploratory treatment arm (neoadjuvant nivolumab plus ipilimumab); enrollment for this arm was closed early and the arm discontinued. (ii) 34 patients who were randomized to chemotherapy in the initial protocol (i.e., before the addition of the nivolumab plus chemotherapy arm) who were not included in the primary analysis population.

FIGURE 2

Event‐free survival (EFS)^a per blinded independent central review (BICR) in Japanese patients with resectable non‐small‐cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy or chemotherapy alone. ^aDefined as the time from randomization to any of the following events: any disease progression precluding surgery, disease progression or recurrence after surgery (based on BICR assessment per RECIST version 1.1), disease progression in the absence of surgery, or death due to any cause; data on patients who received subsequent therapy were censored at the last assessment on or before the start of subsequent therapy during which tumor evaluation could be performed. CI, confidence interval; HR, hazard ratio; mo, months; NR, not reached.

FIGURE 3

(A) Pathological complete response (pCR) and (B) major pathological response (MPR) per blinded independent pathological review in Japanese patients with resectable non‐small‐cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy or chemotherapy alone. ^aPatients who did not undergo surgery were classified as nonresponders. ^bDefined as 0% residual viable tumor cells in both primary tumor (lung) and sampled lymph nodes. 95% confidence interval (CI) for pCR: ^c15.6–48.7; ^d0.7–19.2. ^eDefined as ≤10% residual viable tumor cells in both primary tumor (lung) and sampled lymph nodes. 95% CI for MPR: ^f22.9–57.9; ^g3.2–26.7. OR, odds ratio.

FIGURE 4

Depth of pathological response in the primary tumor in Japanese patients^a with resectable non‐small‐cell lung cancer: (A) nivolumab plus chemotherapy arm, n = 29 and (B) chemotherapy arm, n = 29. ^aOnly patients who underwent definitive surgery and had an evaluable pathology sample for blinded independent pathological review were included. IQR, interquartile range; pCR, pathological complete response; RVT, residual viable tumor.

FIGURE 5

Event‐free survival (EFS2)^a in Japanese patients with resectable non‐small‐cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy or chemotherapy alone. ^aDefined as the time from randomization to the first of the following events: objectively documented progression per investigator assessment, after the next line of therapy or death from any cause; patients without documented progression on the next line who started a second next line of subsequent therapy were considered to have had an event at the start of second next line of therapy. CI, confidence interval; HR, hazard ratio; mo, months; NR, not reached.

FIGURE 6

Time to death or distant metastases^a in Japanese patients with resectable non‐small‐cell lung cancer treated with neoadjuvant nivolumab plus chemotherapy or chemotherapy alone. ^aDefined as the time from randomization to the first occurrence of distant metastases or death, whichever occurs first. CI, confidence interval; HR, hazard ratio; mo, months; NR, not reached.