“The combination of atezolizumab (Tecentriq) and cobimetinib (Cotellic) may lead to a higher overall response (ORR) and a longer progression-free survival (PFS) than either agent alone in patients with metastatic melanoma, according to findings presented at the 2016 Society for Melanoma Research (SMR) Annual Meeting.
“The findings were part of a phase Ib dose-escalation and dose-expansion study, which looked at the PD-L1 inhibitor and MEK inhibitor together in advanced solid tumors. Data on a cohort of 22 patients with ocular melanoma (n = 2) and non-ocular melanoma (n = 20) was presented at the meeting. Among patients in the non-ocular cohort, the ORR was 45% and the disease-control rate (complete response, partial response, and stable disease) was 75%. Median PFS was 12 months (95% CI, 2.8-16.7).”
As always, the more new treatments become available in melanoma, the more new challenges arise. With eight new drugs approved for melanoma in the last five years, oncologists may sometimes face the difficult choice of what drugs to choose for a patient’s first-line treatment. Immune checkpoint drugs sometimes cause serious side effects, but progress is being made on how to treat these and also how to treat patients with pre-existing autoimmune conditions. New approaches are needed in efforts to prevent recurrence of melanomas diagnosed at earlier stages of disease progression. These and other challenges are discussed below. Continue reading…
“Indications for the blockbuster cancer drug nivolumab (Opdivo) have expanded again, as the FDA has approved the anti-PD-1 antibody in combination with ipilimumab (Yervoy) for treatment of unresectable or metastatic melanoma.
“The indication includes both BRAF-wild type and BRAF-mutant melanoma. At the same time, the FDA expanded the indication for single-agent nivolumb to include patients with previously untreated BRAF-wild type melanoma.
“Granted by the FDA’s accelerated approval process, the indication is the seventh for nivolumab, both indications leave the door open for the FDA to request confirmatory data or clinical trials. The approvals increase the number of nivolumab indications to seven, including four in melanoma, all granted since late 2014.”
“The approval was based on a substantial improvement in overall survival (OS) in a phase 3 study.
“The FDA has expanded the approval for single-agent Opdivo (nivolumab) to include the frontline treatment of patients with BRAF wild-type advanced melanoma, based on a substantial improvement in overall survival (OS) compared with the chemotherapy dacarbazine in a phase 3 study.
“In the data assessed by the FDA from the CheckMate-066 trial, the median OS with Opdivo was not reached versus 10.8 months for dacarbazine, representing a 58 percent reduction in the risk of death. Median progression-free survival (PFS) with Opdivo was 5.1 versus 2.2 months for dacarbazine.”
“Bristol-Myers Squibb Company (NYSE:BMY) today announced new long-term data of Opdivo in treatment-naïve BRAF wild-type advanced melanoma from CheckMate -066. In the trial, Opdivo continued to demonstrate superior overall survival versus dacarbazine with 57.7% of patients alive at two years compared to 26.7% of patients treated with dacarbazine. The safety profile of Opdivo was consistent with prior studies. The two-year survival and safety data from CheckMate -066 represent the longest follow-up from a randomized study of any PD-1 immune checkpoint inhibitor in the first-line setting of advanced melanoma. These data will be presented as a late-breaking presentation at the Society for Melanoma Research (SMR) 2015 International Congress in San Francisco, CA from November 18 to 21.”
“The review period for frontline nivolumab (Opdivo), in patients who have advanced melanoma, recently received an extension of 3 months by the FDA, in order to allow ample time for review of the additional data submitted by Bristol-Myers Squibb (BMS). The updated action date for the new indication is November 27, 2015.
“Nivolumab initially received a priority review designation for the new indication on April 30, 2015, based on the phase III CheckMate-066 trial that explored nivolumab in untreated patients with BRAF wild-type advanced melanoma. The new data hope to support an approval that is irrespective of BRAF status, BMS indicated.
“ ‘The CheckMate-066 trial marked the first time that a PD-1 immune checkpoint inhibitor showed a survival benefit in a randomized phase III trial,’ Michael Giordano, MD, senior vice president, Head of Development, Oncology, BMS, said when the FDA initially accepted the application. ‘We look forward to continuing to work with the FDA to ensure cancer patients are provided the latest clinical advances that have the potential for improved responses and long-term survival.’ “
“A pooled analysis of four clinical trials of nivolumab (Opdivo) in advanced melanoma, reported by Larkin et al in JAMA Oncology, suggested similar response rates in patients with BRAF V600 mutant and BRAF wild-type disease.
“The retrospective analysis included data from adult patients with unresectable stage III or stage IV melanoma from four clinical trials. Nivolumab was given at 0.1, 0.3, 1.0, 3.0, or 10.0 mg/kg every 2 weeks until disease progression, treatment discontinuation due to adverse events, withdrawal, or end of study, with 83% of patients receiving the 3 mg/kg dose. Overall, 72% of patients in the BRAF mutant group had received prior BRAF inhibitor therapy. A total of 73% of patients in the BRAF wild-type group and 86% in the mutant group had received at least two prior therapies for advanced disease.
“The investigators concluded, ‘The results of this retrospective analysis suggest that nivolumab has similar efficacy and safety outcomes in patients with wild-type or mutant BRAF, regardless of prior BRAF inhibitor or ipilimumab treatment.’ “
“Yale University has launched a multicenter clinical trial, sponsored by Stand Up to Cancer and Melanoma Research Alliance, that will apply the latest in personalized medicine technology to treat metastatic melanoma. The trial, for which Yale is a lead site, will enroll patients lacking a particular genetic mutation for whom immune therapy did not work or was not an option.
“Metastatic melanoma is a type of cancer that has spread from the skin to other parts of the body, most frequently the lungs, muscle, and liver. It is the most advanced and deadly type of melanoma, and notoriously difficult to treat.
” ‘Metastatic melanoma is one of those cancers for which we have distressingly few treatment options after immune therapy has failed,’ said Patricia M. LoRusso, associate director of Innovative Medicine at Yale Cancer Center and national co-principal investigator of the Melanoma Dream Team. ‘This partnership of cancer centers, research organizations, and industry offers the best chance we’ve had in long time to find solutions for melanoma patients. We think the personalized medicine approach is the way forward.’ “
The gist: A recent clinical trial with volunteer patients compared two treatments for metastatic melanoma. It showed that one of the treatments might give longer survival times for people whose tumors do not have mutations in the BRAF gene. This treatment is a drug called nivolumab. It is an immunotherapy drug, meaning that it boosts a patient’s own immune system to fight cancer. In the trial, some patients took nivolumab and some took the chemotherapy drug dacarbazine. People who took nivolumab lived a few months longer than people who took dacarbazine. None of the patients had taken any previous treatments for their melanoma.
“Patients with treatment-naive, BRAF wild-type metastatic melanoma treated with nivolumab demonstrated longer OS and PFS than those treated with dacarbazine, according to phase 3 study results presented at the Society for Melanoma Research International Congress.
“Prior research showed nivolumab (Opdivo, Bristol-Myers Squibb) — a PD-1 immune checkpoint inhibitor — was associated with higher rates of objective response compared with chemotherapy in patients with ipilimumab (Yervoy, Bristol-Myers Squibb)-refractory disease.
“In the current study, Caroline Robert, MD, PhD, head of the Dermatology Unit at the Institut Gustave-Roussy in Paris, and colleagues compared the efficacy of nivolumab vs. chemotherapy in 418 previously untreated patients.
“Researchers assigned patients 3 mg/kg nivolumab every 2 weeks plus a dacarbazine-matched placebo, or 1,000 mg/m2dacarbazine every 3 weeks plus a nivolumab-matched placebo.”