On October 3, 2024, the Food and Drug Administration sanctioned nivolumab (Opdivo, Bristol Myers Squibb Company) in conjunction with platinum-doublet chemotherapy as neoadjuvant therapy, succeeded by single-agent nivolumab post-surgery as adjuvant therapy, for adults with resectable non-small cell lung cancer (NSCLC) characterized by tumors ≥ 4 cm and/or node positivity, and devoid of known epidermal growth factor receptor (EGFR) mutations or anaplastic lymphoma kinase (ALK) rearrangements.
Efficacy and Safety
The efficacy was assessed in CHECKMATE-77T (NCT04025879), a randomized, double-blind, placebo-controlled multicenter trial involving 461 patients with previously untreated and resectable non-small cell lung cancer (NSCLC) at Stage IIA to selected Stage IIIB (AJCC, 8th edition). Patients were randomized (1:1) to receive either nivolumab or placebo, in conjunction with platinum-based chemotherapy, administered every 3 weeks for a maximum of 4 cycles (neoadjuvant treatment), followed by either ongoing single-agent nivolumab or placebo every 4 weeks for up to 13 cycles (adjuvant treatment).
The primary efficacy outcome measure was event-free survival (EFS) assessed by blinded independent central review. The median event-free survival (EFS) was not attained (95% CI: 28.9, not estimable [NE]) in the nivolumab group, while it was 18.4 months (95% CI: 13.6, 28.1) in the chemotherapy group (hazard ratio 0.58 [95% CI: 0.43, 0.78]; p-value 0.00025). During the predetermined interim analysis, overall survival (OS) was not subjected to rigorous statistical significance testing; yet, a descriptive analysis indicated no adverse effects.
Adverse effects were comparable to those observed in other clinical trials, including nivolumab and chemotherapy. Among those administered neoadjuvant nivolumab, 5.3% were precluded from surgery due to adverse effects, in contrast to 3.5% in the placebo group. Furthermore, 4.5% of patients who underwent neoadjuvant treatment and surgery in the nivolumab group experienced surgical delays due to side effects, in contrast to 3.9% in the placebo group. Refer to the prescription instructions for further safety details.
The advised dosage of nivolumab is 360 mg every three weeks for neoadjuvant treatment and 480 mg every four weeks for adjuvant treatment. Nivolumab must be delivered before chemotherapy when given on the same day.
This evaluation was performed under Project Orbis, a program of the FDA Oncology Center of Excellence. Project Orbis offers a framework for the simultaneous submission and evaluation of oncology treatments among global collaborators. For this evaluation, the FDA partnered with the Australian Therapeutic Goods Administration (TGA), the Brazilian Health Regulatory Agency (ANVISA), Health Canada, and Israel’s Ministry of Health (IMoH). The application evaluations are currently in progress at the other regulatory bodies.
Dr. Nishant Mittal is a highly accomplished researcher with over 13 years of experience in the fields of cardiovascular biology and cancer research. His career is marked by significant contributions to stem cell biology, developmental biology, and innovative research techniques.
Research Highlights
Dr. Mittal's research has focused on several key areas:
1) Cardiovascular Development and Regeneration: He studied coronary vessel development and regeneration using zebrafish models1.
2) Cancer Biology: At Dartmouth College, he developed zebrafish models for studying tumor heterogeneity and clonal evolution in pancreatic cancer.
3) Developmental Biology: His doctoral work at Keio University involved identifying and characterizing medaka fish mutants with cardiovascular defects.
4) Stem Cell Research: He investigated the effects of folic acid on mouse embryonic stem cells and worked on cryopreservation techniques for hematopoietic stem cells.
Publications and Presentations
Dr. Mittal has authored several peer-reviewed publications in reputable journals such as Scientific Reports, Cardiovascular Research, and Disease Models & Mechanisms1. He has also presented his research at numerous international conferences, including the Stanford-Weill Cornell Cardiovascular Research Symposium and the Weinstein Cardiovascular Development Conference.
In summary, Dr. Nishant Mittal is a dedicated and accomplished researcher with a strong track record in cardiovascular and cancer biology, demonstrating expertise in various model systems and a commitment to advancing scientific knowledge through innovative research approaches.
