Immunotherapy + Chemo Boosts Response for NSCLC patients with resectable tumors, new study out of Johns Hopkins University, Baltimore shows.

Immunotherapy + Chemo boosts response: Neoadjuvant chemotherapy with nivolumab plus platinum-doublet chemotherapy significantly improved pathologic complete response rates compared with chemotherapy alone in patients with resectable stage IB to IIIA non–small cell lung cancer (NSCLC), according to the results of the CheckMate 816 study presented at the virtual edition of the American Association for Cancer Research (AACR) Annual Meeting 2021.1 The pathologic complete response rate was 24% with nivolumab plus chemotherapy vs 2.2% with chemotherapy. In the trial, pathologic complete response was the primary endpoint, and pathologic complete response to neoadjuvant therapy has been associated with improved survival in retrospective studies.

“The standard treatment of 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,” explained lead author ­Patrick M. Forde, MBBCh, Associate Professor at the Sidney Kimmel Comprehensive Cancer Center and Bloomberg-Kimmel Institute for Cancer Immunotherapy at Johns Hopkins University, Baltimore.

“For the first time in a phase III trial, we see the potential for an anti–PD-L1 immunotherapy to improve outcomes in earlier-stage NSCLC. We are highly encouraged by the marked improvement in pathologic complete response, the good overall tolerability, and the absence of impact on the feasibility of surgery when nivolumab is added to neoadjuvant chemotherapy,” stated Dr. Forde.

“The significant improvement in pathologic complete response and absence of any meaningful increase in toxicity or decrease in the feasibility of surgery suggest that neoadjuvant nivolumab plus chemotherapy is a viable option for patients with NSCLC at high risk of recurrence. Although neoadjuvant chemotherapy has historically been less commonly used than adjuvant chemotherapy for this patient population, I believe CheckMate 816 has the potential to change that treatment paradigm,” Dr. Forde told listeners.

Description of Study: Immunotherapy + Chemo Boosts Response in Resectable NSCLC

Platinum-based neoadjuvant or adjuvant chemotherapy for resectable NSCLC improves survival by just 5% at 5 years. “Several studies suggest a clear association between pathologic complete response and overall survival. Of note, patients with resectable NSCLC treated with neoadjuvant chemotherapy have had low rates of pathologic complete response, a median of 4%, ranging from 0% to 16%,” Dr. Forde said. More recently, single-arm phase II studies of immunotherapy as monotherapy or in combination have yielded encouraging results, leading to the phase III CheckMate 816 trial.

Dr. Forde presented the final analysis of pathologic complete response and key secondary endpoints in the randomized, open-label CheckMate 816 trial; this study evaluated nivolumab plus chemotherapy vs chemotherapy alone as neoadjuvant treatment in 358 newly diagnosed patients with resectable stage IB to IIIA NSCLC. No sensitizing EGFR or ALK mutations were allowed. Patients were stratified by cancer stage, PD-L1 status, and gender.

Baseline characteristics were well balanced between the two treatment arms. About two-thirds had stage IIIA disease, and participants were evenly split between squamous and nonsquamous histologies. Tumor mutational burden results were available for 50%.

Patients were randomly assigned 2:1 to receive nivolumab at 360 mg every 3 weeks plus chemotherapy every 3 weeks (three cycles) vs the same chemotherapy schedule. Then, patients underwent radiologic staging and surgery within 6 weeks of neoadjuvant therapy. They had the option of adjuvant therapy with or without radiation therapy. An exploratory arm of nivolumab plus ipilimumab was closed early.

The primary endpoint was pathologic complete response by blinded independent review, defined as no residual viable tumor in resected primary tumor and lymph nodes after surgery. Event-free survival was a co-primary endpoint but was not presented at the AACR meeting.

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