Nivolumab Gains European Approval for Squamous NSCLC

Rolf Stahel, MD

The European Commission has approved nivolumab (Opdivo) as a treatment for patients with locally advanced or metastatic squamous non—small cell lung cancer (NSCLC) following prior chemotherapy, based on findings from the phase III CheckMate-017 and the phase II CheckMate-063 trials.

In the phase III CheckMate-017 trial, nivolumab improved overall survival (OS) by 3.2 months versus docetaxel in previously treated patients with squamous NSCLC. In the smaller, single-arm phase II CheckMate-063 study, nivolumab demonstrated a median OS of 8.2 months and a 1-year OS rate of 41%.

The PD-1 inhibitor is the first agent approved for patients in Europe with squamous NSCLC in over a decade. The European Commission decision follows a recommendation from Committee for Medicinal Products for Human Use, and allows for the medication to be marketed across 28 European Union member states.

“Today’s approval of nivolumab for squamous non-small cell lung cancer is truly a major advance for patients fighting this devastating disease, and the providers that treat them,” Rolf Stahel, MD, president of the ESMO and professor at University Hospital Zurich, said in a statement. “Nivolumab has shown statistically significant and clinically meaningful improvement in efficacy versus standard of care in this patient population. This approval reinforces the science behind Immuno-Oncology including our understanding of the role of PD-L1 expression.”

In the phase III open-label CheckMate-017 study, 272 pretreated patients with squamous NSCLC were randomized to receive nivolumab at 3 mg/kg every 2 weeks (n = 135) or docetaxel at 75 mg/m² every 3 weeks (n = 137). The primary endpoint of the trial was OS. Secondary outcome measures included objective response rates (ORR; RECIST v1.1), progression-free survival (PFS), safety, and outcomes by PD-L1 expression.

According to findings published in The New England Journal of Medicine, the median OS was 9.2 months with nivolumab versus 6.0 months with chemotherapy (HR = 0.59; P = .00025). The 1-year OS was 42% versus 24% for nivolumab and docetaxel, respectively. The median PFS with nivolumab was 3.5 months compared with 2.8 months (HR = 0.62; 95% CI, 0.47-0.81; P = .0004).

The ORR with nivolumab was 20% compared with 9% for chemotherapy (P = .0083). The median duration of response was 8.4 months in the docetaxel arm and had not yet been reached in patients receiving nivolumab.

Regardless of tumor PD-L1 levels, OS favored nivolumab. In PD-L1—positive patients (≥1% of tumor cells express PD-L1), median OS was improved by 31% (HR = 0.69) with nivolumab versus a 42% benefit with the PD-1 inhibitor (HR = 0.58) in the PD-L1–negative group.

In evaluable patients, grade 3/4 adverse events (AEs) were reported in 6.9% of patients in the nivolumab arm versus 55% of those who received chemotherapy. There were no treatment-related deaths in the nivolumab cohort compared with 3 deaths linked to docetaxel (2.3%). All-grade AEs occurred in 58% and 86% of patients, in the nivolumab and docetaxel arms, respectively. Overall, 3.1% of patients in the nivolumab arm discontinued treatment due to an AE compared with 10.1% for docetaxel.

Findings from the CheckMate-063 study were similar to those from the larger CheckMate-017 trial. The ORR in the phase II study was 14.5% with nivolumab. Additionally, the safety profile was consistent between the two studies.

“With the EU approval of nivolumab, patients in Europe have for the first time in more than ten years access to an entirely new treatment modality for advanced squamous non-small cell lung cancer, which has the potential to replace the current standard of care,” Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb, the company developing the biologic, said in a statement. “Bristol-Myers Squibb is passionate about changing survival expectations and the way patients live with advanced cancers, and is committed to continually deliver, with speed and urgency, new approaches to pursue this goal.”

The NSCLC indication adds to the growing list of approvals for nivolumab, which was the first PD-1 inhibitor to gain approval worldwide, with an initial indication for melanoma in Japan. In Europe, the agent was approved as a treatment for patients with advanced melanoma in the first- and later-line setting regardless of BRAF mutation status in June 2015.

In the United States, nivolumab is FDA-approved for the treatment of patients with unresectable or metastatic melanoma following treatment with ipilimumab or a BRAF inhibitor. In addition to melanoma, the FDA approved nivolumab in March 2015 as a treatment for patients with metastatic squamous NSCLC following a platinum-based chemotherapy.

Brahmer J, Reckamp KL, Baas P, et al. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non—Small-Cell Lung Cancer. N Engl J Med. 2015; 373:123-135.