FDA Approves Nivolumab With Chemotherapy for Neoadjuvant Treatment of Resectable Non-Small Cell Lung Cancer


Nivolumab (Opdivo) plus platinum-doublet chemotherapy approved for the treatment of adult patients with resectable non–small cell lung cancer in the neoadjuvant setting.

The FDA has approved nivolumab (Opdivo) plus platinum-doublet chemotherapy for the treatment of adult patients with resectable non–small cell lung cancer (NSCLC) in the neoadjuvant setting.

The approval was based on findings from the phase 3 CheckMate-816 trial, which showed that the nivolumab combination (n = 179) produced a significant improvement in event-free survival (EFS) compared with chemotherapy alone (n = 179). The median EFS with nivolumab plus chemotherapy was 31.6 months (95% CI, 30.2–not reached) compared with 20.8 months (95% CI, 14.0-26.7) with chemotherapy alone (hazard ratio [HR], 0.63; 95% CI, 0.45-0.87; =.0052).

Furthermore, the nivolumab combination produced a pathologic complete response (pCR) of 24% (95% CI, 18.0%-31.0%) compared with 2.2% (95% CI, 0.6%-5.6%) with chemotherapy alone (estimated treatment difference 21.6; 95% CI, 15.1-28.2; < .0001). A prespecified interim analysis of overall survival (OS) resulted in an HR of 0.57 (95% CI, 0.38-0.87), which was not statistically significant, according to the investigators.

“Given the rates of disease recurrence in patients with resectable NSCLC, additional treatment options are needed that can be given before surgery to help improve the chance of successful surgical treatment and support the goal of reducing the risk of cancer returning,” said Mark Awad, MD, PhD, CheckMate-816 study investigator and clinical director of the Lowe Center for Thoracic Oncology at Dana-Farber Cancer Institute, in a press release. “The approval of nivolumab with platinum-doublet chemotherapy marks a turning point in how we treat resectable NSCLC and it enables us to use immunotherapy and chemotherapy as neoadjuvant treatment for patients before surgery. Today’s announcement reinforces the need to increase the rates of NSCLC screening and early detection, and for patients to discuss treatment options with their providers.”

CheckMate-816, an open-label, multicenter, phase 3 trial, enrolled patients with newly diagnosed, resectable, stage IB to IIIA NSCLC with an ECOG performance status of 0 or 1 and no known sensitizing EGFR mutations or ALK alterations.

The trail randomized 358 participants 1:1 to receive nivolumab 360 mg every 3 weeks plus platinum-doublet chemotherapy every 3 weeks for 3 doses, or chemotherapy alone. Patients then received radiologic restaging, and had surgery within 6 weeks post treatment, went on to receive optional adjuvant chemotherapy with or without radiotherapy, and then entered follow-up.

Patients were stratified by disease stage (IB/II vs IIIA), PD-L1 expression (1% or higher vs less than 1%), and sex (male vs female).

The primary end points of the trial were pCR by blinded independent pathological review (BIPR), and EFS by blinded independent central review (BICR). Key secondary end points included major pathological response by BIPR, overall survival, and time to death or distant metastases. Exploratory end points were objective response rate by BICR, and feasibility of surgery as well as peri- and post-operative surgery–related toxicities.

At the database lock date of September 16, 2020, with a minimum follow-up of 7.6 months for both cohorts, 179 patients were randomized to receive nivolumab/chemotherapy and 179 received chemotherapy alone, with 98% of patients in both arms administered neoadjuvant treatment. Among patients in the investigative cohort, 94% completed 3 cycles of the neoadjuvant treatment compatrf with 85% in the control cohort.

Furthermore, 16% of patients in the investigative cohort cancelled surgery due to progressive disease (7%), toxicity (1%), or an unspecified reason (8%). Of patients in the control group, 21% cancelled their surgery, 10% of whom did so due to disease progression, 1% due to an adverse effect, and 11% due to another reason. In the investigative cohort, 83% of patients received surgery compared with 75% in the control group. The median duration of surgery among these cohorts was 184 minutes and 217 minutes, respectively.

The median age of patients on the nivolumab/chemotherapy cohort was 64 years (range, 41-82) compared with 65 years (range, 34-84) in the chemotherapy-alone cohort; 28% and 29% of patients, respectively, were female, and 69% and 65% of patients, respectively, had an ECOG performance status of 0.

In the nivolumab/chemotherapy cohort, 49% had squamous disease and 51% had nonsquamous disease compared with 53% and 47%, respectively, in the control group. Most of the patients were current or former smokers.

For adverse events (AEs), nivolumab is linked to severe and fatal immune-mediated AEs, including pneumonitis, colitis, hepatitis and hepatotoxicity, endocrinopathies, dermatologic adverse reactions, nephritis with renal dysfunction, other immune-mediated AEs, infusion-related reactions, complications of allogeneic hematopoietic stem cell transplantation, and embryo-fetal toxicity.

“At Bristol Myers Squibb, we are leading innovative science in the use of immunotherapy in earlier stages of cancer and are committed to bringing these options to patients,” Adam Lenkowsky, senior vice president and general manager, US Cardiovascular, Immunology and Oncology at Bristol Myers Squibb, added in the press release. “Today’s approval builds on that commitment and expands the role of nivolumab-based treatment in NSCLC, the most common form of lung cancer, so patients may benefit earlier in the course of their disease.”


US Food and Drug Administration approves Opdivo (nivolumab) with chemotherapy as neoadjuvant treatment for certain adult patients with resectable non-small cell lung cancer. News release. Bristol Myers Squibb; March 4, 2022. Accessed March 4, 2022. https://bit.ly/3sG3zQA

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