Nivolumab demonstrates superiority to chemotherapy for advanced melanoma

Source: Healio.com/Oncology, March 2015

Nivolumab was associated with a greater objective response rate and an improved toxicity profile compared with chemotherapy in patients with advanced melanoma who had progressed after anti-cytotoxic T-lymphocyte antigen-4 treatment, according to the results of a randomized, open-label, phase 3 trial.

“Nivolumab is clearly a superior choice in term of response rate and toxicity to chemotherapy for patients who have failed prior ipilimumab, or ipilimumab and a BRAF inhibitor if the patient is BRAF-mutated,” study researcher Jeffrey S. Weber, MD, PhD, of the Moffitt Cancer Center in Tampa, Florida, told HemOnc Today.

Data from previous phase 1 and phase 2 studies suggested that nivolumab (Opdivo, Bristol-Myers Squibb) — a fully human immunoglobulin G4 programmed cell death 1 (PD-1) antibody — demonstrated activity in patients with melanoma whose disease progressed after treatment with ipilimumab (Yervoy, Bristol-Myers Squibb). The phase 3 trial was conducted to verify that nivolumab was active, well tolerated and superior to a reference chemotherapy arm, according to study background.

Weber and colleagues randomly assigned 405 patients to 3 mg/kg nivolumab every 2 weeks (n = 272) or investigator’s choice chemotherapy (n = 133).

Men represented a majority of the nivolumab (65%) and chemotherapy (64%) cohorts. The median age of the nivolumab cohort was 59 years (range, 23-88) and the median age of the chemotherapy cohort was 62 years (range, 29-85).

Median treatment duration was longer in the nivolumab arm (5.3 vs. 2 months).

Objective response and OS served as the primary endpoints, and PFS served as the secondary endpoint.

Median follow-up was 8.4 months.

Results of the first interim analysis demonstrated a greater ORR in the nivolumab vs. chemotherapy arm (31.7% vs. 10.6%). Median time to response was 2.1 months (range, 1.6-7.4) in the nivolumab arm and 3.5 months (range, 2.1-6.1) in the chemotherapy arm.

Results of the intention-to-treat objective response analysis indicated median PFS was 4.7 months in the nivolumab arm and 4.2 months in the chemotherapy arm (HR = 0.82; 99.99% CI, 0.32-2.05). A greater proportion of patients who received nivolumab achieved 6-month PFS (48% vs. 34%).

A majority of patients in both arms experienced toxicity. Fatigue, pruritus and diarrhea were the most frequently reported adverse events in the nivolumab arm, whereas nausea, fatigue and alopecia were the most frequently reported adverse events in the chemotherapy arm.

A greater proportion of patients who received chemotherapy experienced a grade 3 to grade 4 adverse event (31% vs. 9%) and a serious adverse event (9% vs. 5%). The most common treatment-related grade 3 to grade 4 adverse events associated with nivolumab were increased lipase (1%), increased alanine aminotransferase (1%), fatigue (1%) and anemia (1%). Common grade 3 to grade 4 adverse events in the chemotherapy arm included neutropenia (14%), thrombocytopenia (6%) and anemia (5%).

The researchers acknowledged greater treatment withdrawal among chemotherapy patients and the need for a longer follow-up time to determine possible changes in overall PFS are limitations of the current analysis.

“We await the final survival analysis, which requires more follow-up time to mature,” Weber said.  “Follow-up trials with nivolumab will include novel combinations with other promising immunotherapies, and development of crucially needed predictive biomarkers for outcome with nivolumab.” – by Cameron Kelsall

For more information:

Jeffrey S. Weber, MD, PhD, can be reached at Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612; email: jeffrey.weber@moffitt.org.
Disclosure: Weber reports stock ownership in Altor BioScience, Celldex Therapeutics and cCAM Biotherapeutics; honoraria and research funding from AbbVie, AstraZeneca, Bristol-Myers Squibb, Genentech, GlaxoSmithKline, Genentech, Merck and Macrogenics; and paid advisory roles with Ichor Therapeutics, Lion Biotechnologies and Pieris. Please see the full study for a list of all other researchers’ relevant financial disclosures.