“The combination of the programmed death receptor 1 (PD-1) inhibitor nivolumab at a reduced dose (1 mg/kg) with the cytotoxic T-lymphocyte antigen 4 (CTLA-4) inhibitor ipilimumab at standard dose (3 mg/kg) for four doses followed by standard-dose nivolumab alone is a standard of care for patients with advanced, previously untreated melanoma. This is based on results from the phase III CheckMate-067 trial that confirmed combination therapy is significantly more effective than single-agent nivolumab or ipilimumab. However, improvement in efficacy is associated with increased treatment-related grade 3/4 adverse events and treatment discontinuation in nearly 40% of patients.”
“Matthew D. Hellmann, MD, medical oncologist, Memorial Sloan Kettering Cancer Center, discusses the CheckMate-032 study, which explored nivolumab (Opdivo) with or without ipilimumab (Yervoy) for patients with small cell lung cancer (SCLC).”
“The addition of T-VEC (T-VEC; Imlygic), a herpes simplex virus 1-based oncolytic virus, to CTLA-4 inhibitor ipilimumab (Yervoy) improves the objective response rate (ORR) in patients with unresected stage IIIb to IV melanoma, according to findings presented at the 7th European Post-Chicago Melanoma/Skin Cancer Meeting.
“T-VEC was the first approved oncolytic virus therapy in Europe, the United States, and Australia, and its efficacy was previously demonstrated in a phase III trial comprising patients with advanced unresectable melanoma.”
“Bristol-Myers got a much-needed boost with the earlier-than-expected news that Opdivo beat out Yervoy in a Phase III study focused on a particular niche for adjuvant melanoma therapy. And an analyst who’s been following the data says it could be worth a billion dollars in added annual sales.
“The big biotech says an interim analysis of Checkmate-238 provided researchers with proof that the PD-1 drug outperformed Yervoy, Bristol-Myers’ CTLA-4 drug, among advanced Stage IIIb or IV patients, cutting the recurrence rate for those who have undergone surgery. There are no bottom line numbers in the statement, but Bristol-Myers says they’ll be able to release data at an upcoming conference to show that Opdivo provided a significantly lower risk of disease recurrence.”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
“In the phase III CA184-095trial reported in the Journal of Clinical Oncology, Tomasz M. Beer, MD, FACP, of the Knight Cancer Institute, Oregon Health and Science University, and colleagues found that ipilimumab (Yervoy) did not increase overall survival vs placebo in men with asymptomatic or minimally symptomatic chemotherapy-naive metastatic castration-resistant prostate cancer without visceral metastases. Ipilimumab was associated with prolonged progression-free survival and a higher prostate-specific antigen (PSA) response rate.”
“Nivolumab plus ipilimumab demonstrated an intracranial response (ICR) rate of 42% in asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain.
“In the phase II Anti-PD1 Brain Collaboration (ABC) trial, the 6-month intracranial PFS rate was 46% with the anti–PD-1/CTLA-4 combination.
” ‘The combination of nivolumab and ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients,’ said lead author Georgina V. Long, BSc, PhD, MBBS, clinical researcher at the Melanoma Institute Australia and Westmead Hospital in Sydney.”
“Combination treatment with an intratumoral injection of Coxsackievirus A21 (CVA21) and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab has demonstrated durable response with minimal toxicity among patients with advanced melanoma, according to data (abstract CT114) presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, held April 1–5 in Washington, DC.
“Response to the combination occurred even among several patients whose melanoma had progressed despite prior treatment with an immune checkpoint inhibitor.”
“Bristol-Myers Squibb Company (NYSE:BMY) today announced the first overall survival (OS) data from the Phase 3 CheckMate -067 clinical trial. With a minimum follow-up of 28 months, the median OS had not yet been reached in either of the two Opdivo treatment groups and was 20 months for the Yervoy monotherapy group (95% CI: 17.1-24.6). Opdivo in combination with Yervoy and as a monotherapy reduced the risk of death 45% [hazard ratio (HR) 0.55; 95% CI: 0.42-0.72; P<0.0001] and 37% (HR 0.63; 95% CI: 0.48-0.81; P<0.0001), respectively, compared with Yervoy alone. The two-year OS rates were 64% for the Opdivo plus Yervoy combination, 59% for Opdivo alone and 45% for Yervoy alone. Results will be presented today in the press program and an oral presentation during the Update, Novel Indication, and New Immuno-oncology Clinical Trials session from 3:35 to 3:50 p.m. ET (Late-Breaking Abstract CT075) at the American Association for Cancer Research Meeting 2017 in Washington, D.C.”