“Although nivolumab (Opdivo) and ipilimumab (Yervoy) together demonstrate superior survival in previously untreated patients with advanced melanoma, the combination comes with additional toxicity and an increased price tag, says Jason Luke, MD, assistant professor of Medicine at the University of Chicago Medicine.
“ ‘There have been several studies designed around trying to predict which patients are most likely to benefit from anti–PD-1 or immunotherapy combinations. I really think that is going to be an essential part of the future approach to treatment, says Luke. ‘Not all patients respond to these treatments. There are additional toxicities with the combinations, and there are also cost issues because of how catastrophically expensive these drugs are. We really need to know which patients are most likely to respond and which aren’t.’ “
Large numbers of immune cells (T cells in particular) are frequently found within or adjacent to melanoma tumors, indicating that the tumors attract the attention—if not the action—of the immune system. True to its reputation as one of the most ‘immunogenic‘ cancers, melanoma now has more U.S. Food and Drug Administration (FDA)-approved immunotherapy (immune system-targeting) drugs than any other cancer type. As a consequence, metastatic melanoma is no longer the universally fatal disease it was even just 3 or 4 years ago. Continue reading…
“The FDA has expanded the approval for single-agent pembrolizumab (Keytruda) to include the frontline treatment of patients with advanced melanoma regardless of BRAF status, based on a substantial improvement in progression-free and overall survival compared with ipilimumab (Yervoy) in the phase III KEYNOTE-006 trial.
“In the study, which compared 2 pembrolizumab regimens with ipilimumab, the PD-1 inhibitor reduced the risk of disease progression by >40% and the risk of death by >30%.
“ ‘As recently as five years ago, there were few treatment options for patients suffering from advanced melanoma,’ Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, the developer of the PD-1 inhibitor, said in a statement. ‘Today’s news is another exciting milestone for Keytruda and for patients with this disease.’ “
Any type of advanced lung cancer is bad news, but a diagnosis of small cell lung cancer (SCLC) is a particularly grim one to receive. About 30 years have passed since any new treatments for SCLC were developed, and patients’ responses to standard chemotherapy with etoposide and cisplatin are short-lived. Hopefully, this will change soon.
“A combination of pembrolizumab and low-dose ipilimumab appears to be active and to have a better safety profile than a combination of nivolumab and full-dose ipilimumab in advanced melanoma patients, according to a new study presented at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.
“Pembrolizumab is a potent, highly selective, humanized monoclonal antibody against programmed death-1 (PD-1) that has shown robust antitumor activity against several advanced malignancies. In phase I testing, combination therapy with the anti–PD-1 antibody nivolumab and full doses (3 mg/kg) of the anti–CTLA-4 therapy ipilimumab was seemingly associated with improved response rates, but also led to increased toxicities, said Georgina Long, BSc, PhD, MBBS, of the Melanoma Institute Australia in Sydney, Australia.”
“The checkpoint inhibitors pembrolizumab and nivolumab not only prolong survival in advanced melanoma patients but also maintain health-related quality of life (QoL), according to two presentations at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.
“In the international, randomized, open-label phase III KEYNOTE-006 study, the anti–programmed death-1 (PD-1) humanized monoclonal antibody pembrolizumab provided superior overall survival (OS), progression-free survival (PFS), and response, and with less high-grade toxicity compared with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in 834 patients with ipilimumab-naive advanced melanoma who received up to one prior therapy.”
“Immunotherapy targeting the programmed cell death (PD) pathway was associated with better outcomes in patients with metastatic melanoma than any other therapy, a new meta-analysis concludes.
“The meta-analysis was featured in a poster presentation here at the Society for Melanoma Research 2015 Congress.
“Anti-PD-1 agents might be a better choice as a first-line therapeutic option, according to Seongseok Yun, MD, PhD, an internal medicine resident at the University of Arizona Medical Center in Tucson, and Nicole Vincelette, a PhD student from the Mayo Clinic in Rochester, Minnesota.”
“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 combination of ipilimumab and palliative radiation therapy reduced tumor growth and the spread of metastases in some patients with metastatic melanoma, according to prospective, phase 2 study results presented at the ASTRO Annual Meeting.
“Local radiation therapy has the potential to augment the induction of systemic anti-melanoma immune responses when used in combination with systemic anti–CTLA-4 immunotherapy, according to study background.
“Thus, Susan M. Hiniker, MD, instructor in the department of radiation oncology at Stanford University School of Medicine, and colleagues assessed the safety and efficacy of combining ipilimumab (Yervoy, Bristol-Myers Squibb) with palliative radiotherapy in patients with stage IV melanoma. Researchers also assessed the induction of anti-melanoma immune response.
“The analysis included data from 20 patients (men, n = 14) aged 18 to 83 years who had stage IV melanoma. Patients received palliative radiotherapy and 3 mg/kg IV ipilimumab every 3 weeks for four treatment cycles. The radiotherapy was initiated within 5 days of the first ipilimumab treatment at one or two melanoma sites.”