On October 17, 2023 Bristol Myers Squibb (NYSE: BMY) reported three-year follow-up results from exploratory analyses of the Phase 3 CheckMate -816 trial, demonstrating sustained event-free survival (EFS) and promising overall survival (OS) trends with three cycles of Opdivo (nivolumab) in combination with platinum-based chemotherapy for the neoadjuvant treatment of patients with resectable non-small cell lung cancer (NSCLC), regardless of PD-L1 expression levels (Press release, Bristol-Myers Squibb, OCT 17, 2023, View Source;816-Trial/default.aspx [SID1234636059]). Neoadjuvant Opdivo with chemotherapy also showed improvements in pathologic complete response (pCR) and major pathologic response (MPR) over chemotherapy alone in PD-L1 ≥1% and <1% patient populations. The safety profile of the Opdivo-based regimen was consistent across all PD-L1 subgroups. These results will be featured in a late-breaking oral presentation at the European Society of Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 on October 23, 2023, from 8:45 a.m. to 9:55 a.m. EDT / 14:45 to 15:55 CEST (Abstract #LBA57).
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"The three-year results with neoadjuvant nivolumab with chemotherapy are a continuation of the statistically significant and clinically meaningful results we have seen with this regimen in the treatment of resectable non-small cell lung cancer, and they provide hope for patients that they may achieve long-term benefit," said Mariano Provencio Pulla, M.D., Ph.D., Medical Oncology, Hospital Universitario Puerta de Hierro, Madrid, Spain. "It is encouraging to see that this neoadjuvant immunotherapy combination has demonstrated improvements across efficacy measures, regardless of PD-L1 expression levels, including within the PD-L1 negative subgroup that faces high unmet needs and represents approximately 40% of the study population. The CheckMate -816 data clearly indicate the potential for better outcomes for patients with this regimen than chemotherapy alone."
With a median follow-up of 41.4 months in the CheckMate -816 trial, exploratory analyses showed:
OS: While OS remains immature at this follow-up, promising OS trends were seen in both PD-L1 ≥1% and <1% patient populations. For patients with tumor PD-L1 expression ≥1%, Opdivo with chemotherapy reduced the risk of death by 63% (Hazard Ratio [HR] 0.37; 95% Confidence Interval [CI]: 0.20 to 0.71). Three-year OS rates favored neoadjuvant Opdivo with chemotherapy over chemotherapy alone at 85% vs. 66%, respectively. In patients with PD-L1 <1%, Opdivo with chemotherapy reduced the risk of death by 19% (HR 0.81; 95% CI: 0.48 to 1.36), with three-year OS rates being 71% vs. 60%.
EFS: Among patients with tumor PD-L1 expression ≥1%, three-year EFS rates were 72% with neoadjuvant Opdivo with chemotherapy vs. 47% with chemotherapy alone (HR 0.46; 95% CI: 0.28 to 0.77). In patients with tumor PD-L1 expression <1%, EFS rates were 42% with the combination vs. 39% with chemotherapy (HR 0.87; 95% CI: 0.57 to 1.35).
pCR: In patients with PD-L1 ≥1%, pCR rates were 32.6% with neoadjuvant Opdivo with chemotherapy compared to 2.2% with chemotherapy alone. For those with PD-L1 <1%, pCR rates were 16.7% vs. 2.6%, respectively.
MPR: Among patients with PD-L1 ≥1%, MPR rates with neoadjuvant Opdivo with chemotherapy were 44.9% vs. 5.6% with chemotherapy. For patients with PD-L1 <1%, MPR rates were 29.5% with the Opdivo-based regimen and 14.3% with chemotherapy alone.
Definitive Surgery: Definitive surgery rates with Opdivo with chemotherapy vs. chemotherapy were 84% vs. 74% in patients with tumor PD-L1 expression ≥1% and 81% vs. 77% in patients with tumor PD-L1 expression <1%. Of these, complete resection was achieved in 91% vs. 82% and 79% vs. 76% of cases, respectively.
"At ESMO (Free ESMO Whitepaper) this year, we are presenting data from several trials across stages and treatment settings in non-small cell lung cancer, including two studies in resectable disease. This is an area of research that we are heavily committed to, as it presents an important opportunity to treat cancer at earlier stages when the tumor is most responsive to treatment and the patient’s immune system is most intact," said Abderrahim Oukessou, M.D., vice president, thoracic cancers global program lead, Bristol Myers Squibb. "We are thrilled to see consistent results with the neoadjuvant regimen of Opdivo with chemotherapy from the CheckMate -816 study, regardless of PD-L1 expression, which build on the benefits we have already seen that led to multiple approvals of this combination globally. We want to sincerely thank every patient and investigator involved in the clinical trial."
Opdivo and Opdivo-based combinations have shown improved efficacy in the neoadjuvant, adjuvant or perioperative treatment of four earlier-stage tumor types, including lung cancer, bladder cancer, esophageal/gastroesophageal junction cancer and melanoma.
About CheckMate -816
CheckMate -816 is a Phase 3 randomized, open label, multi-center trial evaluating Opdivo with chemotherapy compared to chemotherapy alone as neoadjuvant treatment in patients with resectable stage IB to IIIA non-small cell lung cancer (per the 7th edition American Joint Committee on Cancer/Union for International Cancer Control staging criteria), regardless of PD-L1 expression. For the primary analysis, 358 patients were randomized to receive either Opdivo 360 mg plus histology-based platinum doublet chemotherapy every three weeks for three cycles, or platinum doublet chemotherapy every three weeks for three cycles, followed by surgery. The primary endpoints of the trial are event-free survival and pathologic complete response. Secondary endpoints include overall survival, major pathologic response, and time to death or distant metastases.
About Lung Cancer
Lung cancer is the leading cause of cancer deaths globally. Non-small cell lung cancer (NSCLC) is one of the most common types of lung cancer, representing up to 84% of diagnoses. Non-metastatic cases account for the majority of NSCLC diagnoses (approximately 60%, with up to half of these being resectable), and the proportion is expected to grow over time with enhanced screening programs. While many non-metastatic NSCLC patients are cured by surgery, 30% to 55% develop recurrence and die of their disease despite resection, contributing to a need for treatment options administered before surgery (neoadjuvant) and/or after surgery (adjuvant) to improve long-term outcomes.