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No survival difference between nivolumab and investigator’s choice
Nivolumab produced more durable responses and higher response rates in patients with advanced melanoma compared with investigator’s choice chemotherapy, but did not demonstrate a significant improvement in survival, according to findings published in the Journal of Clinical Oncology.
“There have been major advances in the treatment of advanced melanoma, with the development of agents that have changed clinical practice,” James Larkin, PhD, FRCP, consultant medical oncologist with Royal Marsden NHS foundation trust, and colleagues wrote. “Nivolumab and another PD-1 inhibitor, pembrolizumab, have shown increased efficacy compared with ipilimumab in metastatic melanoma and have now been approved for treatment.”
The researchers stratified patients by PD-L1 expression, BRAF status and best prior cytotoxic T-lymphocyte antigen-4 therapy response. Larkin and colleagues randomly assigned patients to intravenous nivolumab at 3 mg/kg every 3 weeks (n = 272; 99% treated) or investigator’s choice therapy of either 1,000 mg/m2 dacarbazine every 3 weeks or carboplatin area under the curve 6 plus 175 mg/m2 paclitaxel every 3 weeks (n = 133; 77% treated). Patients received treatment until unacceptable toxicity or disease progression. Follow-up was approximately 2 years.
At baseline, 20% of patients in the nivolumab group and 14% in investigator’s choice had brain metastases. More patients in the nivolumab group had increased lactate dehydrogenase levels at baseline (52% vs. 38%).
Forty-one percent of patients in the investigator’s choice group received anti-PD–1 agents, compared with 11% of patients in the nivolumab group. More patients treated with investigator’s choice than nivolumab received ipilimumab (11% vs. 5%).
Median OS was 16 months with nivolumab and 14 months with investigator’s choice (HR = 0.95; 95.54% CI, 0.73-1.24). Patients achieved a median PFS of 3.1 months with nivolumab compared with 3.7 months with investigator’s choice (HR = 1; 95.1% CI, 0.78-1.43). Nivolumab conferred a higher overall response rate (27% vs. 10%), as well as a longer median duration of response (32 months vs. 13 months). Patients in the nivolumab group experienced fewer grade 3 and grade 4 treatment-related adverse events (14% vs. 34%).
Researchers noted that “several confounding factors likely impacted OS,” and emphasized caution in interpreting survival rates. A high proportion of patients in the investigator’s choice group dropped out prior to treatment, and more patients in the nivolumab group had poor prognostic factors.
“Although there were no survival differences between nivolumab and investigator’s choice treatments, nivolumab treatment after progression on ipilimumab with or without a BRAF inhibitor does provide a higher rate of response and more durable responses,” the researchers wrote. “Some situations may still exist that necessitate the use of ipilimumab as first-line therapy and nivolumab provides a safer option with a better maintained quality of life for patients who have experienced failure with prior systemic therapies compared with cytotoxic chemotherapy. Despite the lack of survival advantage, nivolumab remains an effective option for PD-1 inhibitor–naïve patients who experienced failure with ipilimumab and a BRAF inhibitor if BRAF mutated.” – by Andy Polhamus
Disclosure: Larkin reports research funding from Bristol-Myers Squibb, MSD, Novartis and Pfizer, as well as travel, accommodations and expenses from Bristol-Myers Squibb, Eisai, GlaxoSmithKline, MSD, Pfizer and Roche.