Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…
“Skin reactions may affect up to 42% of patients treated with pembrolizumab (Keytruda, Merck & Co, Inc) and could indicate better progression-free survival, according to a retrospective review published online July 29 in JAMA Dermatology.
” ‘Cutaneous adverse events are frequent but mild during pembrolizumab treatment. The development of cutaneous adverse events, especially of hypopigmentation, in patients affected by melanoma, could point toward better treatment response,’ commented first author Martine Sanlorenzo, MD, of the University of California, San Francisco.
“Pembrolizumab is an anti–programmed death-1 drug that has shown promise in treating melanoma, non–small cell lung cancer, and renal cell cancer. The drug is a monoclonal antibody that targets the programmed death–1 (PD-1) receptor on T lymphocytes, which functions in immune inactivation. Tumor cells that express the programmed death ligand–1 (PDL-1) take advantage of the PD-1 receptor to evade the immune response.”
“Rita Nanda, MD, assistant professor of Medicine, associate director, Breast Medical Oncology, The University of Chicago Medicine, discusses the efficacy of pembrolizumab and atezolizumab for the treatment of patients with metastatic triple-negative breast cancer (TNBC).
“Response rates seen with the two immunotherapy agents in two separate clinical trials in a heavily pretreated metastatic population was slightly under 20%, Nanda explains. This is significant due to how heavily pretreated these patients were, she adds.
“Furthermore, these responses were found to be durable and lasted up to 40 weeks. Both pembrolizumab and atezolizumab were shown to be well-tolerated. Patients experienced low-grade toxicities that were easily managed.”
“Clinicians who have been treating patients with melanoma using immunotherapy are warning that autoimmune pneumonitis, sometimes with respiratory distress that necessitates intensive care, is ‘a rare but potentially serious toxic effect’ associated with the new programmed cell death (PD) inhibitors.
“Two such drugs are on the market: nivolumab (Opdivo, Bristol-Myers Squibb) for melanoma and non–small cell lung cancer and pembrolizumab (Keytruda, Merck Sharpe & Dohme) for melanoma. Both list pneumonitis as an adverse event in their product labels.
“The clinicians, with first author Mizuki Nishino, MD, all from Dana Farber/Brigham and Woman’s Hospital in Boston, Massachusetts, report three cases of immune-pneumonitis seen after treatment with nivolumab in a letter published in the July 16 issue of the New England Journal of Medicine.”
“In a randomized phase II KEYNOTE-002 trial reported in The Lancet Oncology, Ribas et al found that treatment with the anti–PD-1 antibody pembrolizumab (Keytruda) prolonged progression-free survival vs investigator-choice chemotherapy in patients with advanced melanoma progressing on ipilimumab (Yervoy) and, if BRAF V600 mutant–positive, a BRAF or MEK inhibitor.
“The open-label trial included 540 patients from 12 countries with progressive disease within 24 weeks after two or more ipilimumab doses and, if BRAF V600 mutant–positive, previous treatment with a BRAF or MEK inhibitor or both. Patients were randomly assigned 1:1:1 between November 2012 and November 2013 to receive pembrolizumab 2 mg/kg (n = 180) or 10 mg/kg (n = 181) every 3 weeks or investigator-choice chemotherapy (n = 179, including 42 to paclitaxel plus carboplatin, 28 to paclitaxel, 13 to carboplatin, 45 to dacarbazine, and 43 to temozolomide)…
“The investigators concluded: ‘These findings establish pembrolizumab as a new standard of care for the treatment of ipilimumab-refractory melanoma.’ “
“The results of a phase 3 trial presented during the Plenary Session at the ASCO Annual Meeting comparing combination nivolumab-ipilimumab treatment to nivolumab alone and ipilimumab alone was one of the most pivotal presentations on melanoma at the 2015 ASCO Annual Meeting.
“A second key melanoma study examined survival of patients undergoing SLNB who did or did not receive CLND. Several physicians shared their insights on the Top Takeaways from these findings with Healio.com.
“Jedd D. Wolchok, MD, PhD, chief of melanoma and immunotherapeutics service and the Lloyd J. Old Chair for Clinical Investigation at Memorial Sloan Kettering Cancer Center and a HemOnc Today Editorial Board member, presented the results of the CheckMate 067 study during the Plenary Session that compared the use of nivolumab alone to ipilimumab alone as well as to nivolumab plus ipilimumab. Nivolumab is a programmed death 1 (PD-1) checkpoint inhibitor and ipilimumab is a cytotoxic T-lymphocyte-associated antigen-4 (CTLA-4) checkpoint inhibitor.
“ ‘The most important data that came out — which is very clear — is that there’s no doubt now in anyone’s mind that anti-PD-1 beats anti-CTLA-4. Whether its nivolumab or pembrolizumab, it’s better than giving ipilimumab front-line,’ Sanjiv S. Agarwala, MD, chief of oncology and hematology at St. Luke’s Cancer Center, professor at Temple University School of Medicine and a HemOnc Today Editorial Board member, told Healio.com. Pembrolizumab is another anti-PD-1 immunotherapy indicated for melanoma.”
The biggest news in melanoma treatment from the 2015 American Society of Clinical Oncology (ASCO) annual meeting was undoubtedly the report from a large, phase III, randomized clinical trial that compared a combination of two ‘checkpoint inhibitor’ drugs—nivolumab (Opdivo) and ipilimumab (Yervoy)—with the same drugs given alone.
In the CheckMate-067 trial, 945 previously untreated patients with unresectable stage III or IV melanoma were assigned to Opdivo alone, Opdivo plus Yervoy, or Yervoy alone. Continue reading…
Small cell lung cancer (SCLC) is a fatal disease that has not seen new drug approvals for the last 17 years. Considering the relative success of ‘immune checkpoint inhibitors’ in non-small cell lung cancer (NSCLC), it is not surprising that several abstracts recently presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting were devoted to clinical trials testing these trendy, immune system-boosting drugs in people with SCLC. Continue reading…