Nivolumab/Ipilimumab Plus Chemotherapy Demonstrates Frontline OS Benefit in NSCLC

Fouad Namouni, MD

Fouad Namouni, MD

Nivolumab (Opdivo) in combination with low-dose ipilimumab (Yervoy) and concomitant chemotherapy demonstrated a benefit in overall survival (OS) compared with chemotherapy alone in patients with previously untreated advanced non—small cell lung cancer (NSCLC), according to interim results from the CheckMate -9LA trial.¹

The OS benefit seen met the primary endpoint of the pivotal phase III trial; additionally, the safety profile of the combination was considered in line with the known profiles of the individual immunotherapy and chemotherapy agents.

Bristol-Myers Squibb Company announced in a press release that further results from the CheckMate -9LA trial would be presented at an upcoming medical meeting and shared with regulatory authorities.

“We are excited by the CheckMate -9LA results, which demonstrate the potential of Opdivo plus low-dose Yervoy to provide a survival benefit to patients with non-small cell lung cancer in the first-line setting when administered concomitantly with a limited course of chemotherapy,” Fouad Namouni, MD, head, Oncology Development, Bristol-Myers Squibb, said in a press release. “These results build on the benefit the combination of Opdivo plus Yervoy has previously shown in first-line melanoma, renal cell carcinoma, and most recently lung cancer, and may provide a new therapeutic option for patients.”

The open-label, multicenter, randomized trial is continuing to investigate the use of nivolumab, ipilimumab, and chemotherapy as a first-line treatment for patients with advanced NSCLC, regardless of PD-L1 expression status (NCT03215706). Enrollment is ongoing and investigators expect to enroll approximately 700 patients.

In the experimental arm, patients received 360 mg nivolumab every 3 weeks plus 1 mg/kg ipilimumab every 6 weeks plus 2 cycles of chemotherapy. Treatment is to be continued for up to 2 years or until disease progression or unacceptable toxicity. In the control arm, patients received up to 4 cycles of chemotherapy followed by optional pemetrexed maintenance therapy, if eligible.

OS was the primary endpoint and secondary endpoints include progression-free survival (PFS) and overall response rate (ORR) in the intention-to-treat population as well as PFS, OS, and ORR by PD-L1 expression and tumor mutational burden.

In recent results of part 1 of the CheckMate 227 trial presented at the 2019 ESMO Congress, the combination of nivolumab and ipilimumab demonstrated a survival benefit compared with chemotherapy in the same patient population of those with previously untreated advanced NSCLC regardless of PD-L1 expression.^2,3

The combination was administered in the CheckMate 227 trial at 3 mg/kg nivolumab every 2 weeks plus 1 mg/kg of ipilimumab was given every 6 weeks in the immunotherapy combination arm.

Overall, the median OS was 17.1 months with the combination compared with 13.9 months with chemotherapy (HR, 0.73; 95% CI, 0.64-0.84). Among patients with PD-L1 expression ≥1%, the median OS was 17.1 months with nivolumab and ipilimumab versus 14.9 months with chemotherapy alone (HR, 0.79; 97.72% CI, 0.65-0.96;P= .007).

References

1. CheckMate -9LA, a Phase 3 Trial Evaluating Opdivo (nivolumab) Plus Low-Dose Yervoy (ipilimumab) Combined with Chemotherapy, Meets Primary Endpoint Demonstrating Superior Overall Survival Compared to Chemotherapy Alone in First-Line Lung Cancer [press release]. Princeton, NJ: Bristol-Myers Squibb Company; October 22, 2019. https://bit.ly/2MBIhyx. Accessed October 22, 2019.
2. Peters S, Ramalingam S, Paz-Ares L, et al. Nivolumab + low-dose ipilimumab versus platinum-doublet chemotherapy as first-line treatment for advanced non—small cell lung cancer: CheckMate 227 part 1 final analysis. Presented at: 2019 ESMO Congress; September 27 to October 1, 2019; Barcelona, Spain. Abstract LBA4.
3. Hellmann MD, Paz-Ares L, Carbo RB, et al. Nivolumab plus ipilimumab in advanced non—small-cell lung cancer [published online September 28, 2019].N Eng J Med.doi: 10.1056/NEJMoa1910231.