CheckMate 017: Nivolumab bests docetaxel in squamous NSCLC

Issue: July 10, 2015

CHICAGO — Nivolumab improved survival outcomes compared with docetaxel in a cohort of patients with squamous non–small cell lung cancer, according to findings presented at the ASCO Annual Meeting.

Perspective from Marina Chiara Garassino, MD; Wallace Akerley, MD

David R. Spigel, MD, an oncologist at the Sarah Cannon Research Institute/Tennessee Oncology in Nashville, and colleagues compared nivolumab (Opdivo, Bristol-Myers Squibb) and docetaxel in a cohort of 272 patients with squamous NSCLC who had failed one previous platinum-based doublet chemotherapy regimen.

Researchers randomly assigned 135 patients 3 mg/kg nivolumab arm every 2 weeks and 137 patients 75 mg/m² docetaxel every 3 weeks until disease progression, discontinuation due to toxicity or other factors.

OS served as the primary endpoint. Investigator-assessed objective response rate (ORR), PFS, efficacy by PD-L1 expression, quality of life and safety served as the secondary outcome measures.

Patients in the nivolumab arm achieved a median OS of 9.2 months (95% CI, 7.3-13.3), whereas the median OS in the docetaxel arm was 6 months (95% CI, 5.1-7.3; HR = 0.59; 95% CI, 0.44-0.79).

Forty-two percent (95% CI, 34-50) of patients in the nivolumab arm achieved 1-year OS compared with 24% (95% CI, 17-31) of patients in the docetaxel arm.

PFS was 3.5 months (95% CI, 2.1-4.9) in the nivolumab arm and 2.8 months (95% CI, 2.1-3.5) in the docetaxel arm (HR = 0.62; 95% CI, 0.47-0.81). More patients assigned nivolumab also achieved 1-year PFS (21% vs. 6%).

Spigel reported an ORR of 20% for nivolumab and 9% for docetaxel (P = .0083). The median duration of response was not reached in patients treated with nivolumab, but was 8.4 months (1.4+ to 15.2+) among those treated with docetaxel.

“The median time to response for both drugs is essentially equivalent,” Spigel said.

Nivolumab demonstrated a survival benefit in patients with 1% or greater PD-L1 expression HR = 0.69; 95% CI, 0.45, 1.05), 5% or greater PD-L1 expression (HR = 0.53; 95% CI, 0.31, 0.89) and 10% or greater PD-L1 expression (HR = 0.5; 95% CI, 0.28, 0.89).

“The survival benefit of nivolumab was independent of PD-L1 expression levels,” Spigel said. “A benefit was seen among patients with 1%, 5% or 10% PD-L1 expression, and the benefit was consistently higher for nivolumab.”

A 7% rate of grade 3 to grade 4 drug-related events occurred among patients treated with nivolumab, whereas 57% of patients receiving docetaxel experienced grade 3 to grade 4 events.

No deaths were related to nivolumab; however, three deaths occurred in the docetaxel arm.

“Nivolumab is the first PD-1 inhibitor to demonstrate a survival benefit vs. standard-of-care docetaxel in previously treated patients with advanced squamous NSCLC,” Spigel said. “Nivolumab demonstrates superiority across all secondary efficacy endpoints.”

Spigel added that safety outcomes were consistent with previous studies. – by Rob Volansky

For more information:

Spigel DL, et al. Abstract 8009. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Disclosure: Spigel reports no relevant financial disclosures. Please see the abstract for a full list of the other researchers’ relevant financial disclosures.

Perspective

Marina Chiara Garassino, MD

Docetaxel is a standard of therapy but is hampered by important toxicity. This was a well-conceived and well-conducted trial showing the superiority of nivolumab vs. docetaxel in squamous cell carcinoma.

However, the estimated follow-up is about 15 months, and the curves are only reliable up to about 15 months. The data are not so informative in the tails, which is an important issue in using this drug. It is unclear whether the tails move up in the next year.

There is potential that nivolumab could out-perform not only docetaxel but also the combination of docetaxel and ramucirumab (Cyramza, Eli Lilly).

Marina Chiara Garassino, MD

Fatebenefratelli and Ophthalmic Hospital

Milan, Italy

Disclosures: Garassino reports a consultant/advisory role with and research funding and travel expenses from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck and Roche.

Perspective

Wallace Akerley, MD

This is the study that got nivolumab on the market and this is the first time physicians in the United States have had a chance to look at the data.
This randomized phase 3 study of a PD-1 inhibitor was stunning in that this agent was effective regardless of whether the PD-L1 biomarker was or was not present. It showed a dramatic improvement in survival from 6 months to 9 months compared with chemotherapy. We saw a 40% decrease in death without any specific biomarker. You can use this targeted agent in everybody with squamous cell lung cancer and it works. The other striking aspect was that severe toxicities in the biologic arm were only 7%, compared with 55% for traditional chemotherapy. This therapy is almost like an antibiotic or a placebo in terms of side effects, but it is extremely active. This changes the whole paradigm. We spend a lot of time managing the side effects of chemotherapy. In this circumstance, there are almost none, and patients are doing much better.

Wallace Akerley, MD

Huntsman Cancer Institute

University of Utah

Disclosures: Akerley reports no relevant financial disclosures.