“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…
“The FDA accepted for review the supplemental biologics license application of pembrolizumab for advanced non–small cell lung cancer, according to a press release from the drug’s manufacturer.
“Further, the FDA granted priority review and breakthrough therapy designation to pembrolizumab (Keytruda, Merck) — a humanized monoclonal antibody that blocks the interaction between programmed cell death-1 (PD-1) and its ligands, PD-L1 and PD-L2 — for advanced NSCLC with a target action date of October 2, 2015.
“The FDA will review the use of pembrolizumab in patients with advanced NSCLC whose disease has progressed on or after platinum chemotherapy and an FDA-approved therapy for epidermal growth factor receptor or ALK genomic tumor aberrations, if present.”
“Drugmakers including Bristol-Myers Squibb Co and Merck & Co are testing which patients will most benefit from new cancer treatments based on a protein found in their tumors, but that guide, known as a biomarker, may be too unreliable, researchers and health experts said.
“Bristol’s Opdivo and Merck’s Keytruda are both therapies designed to block a protein known as Programmed Death receptor (PD-1) that tumors use to evade the body’s natural defenses. Competitors Roche Holding, AstraZeneca and Pfizer also have similar drugs in an earlier stage of development. The drugmakers are conducting clinical trials that test patient tumors for a related protein called PD-L1.
“The new drugs are mainly aimed at patients with so-called solid tumors suffering from diseases including lung cancer and liver cancer. Lung cancer, the most common type, claims 1.8 million new cases each year worldwide. Sales of drugs to block PD-1 could reach $33 billion a year by 2022, according to Morningstar.”
“A new drug that unleashes the body’s immune system to attack tumors can prolong the lives of people with the most common form of lung cancer, doctors reported on Friday, the latest example of the significant results being achieved by this new class of medicines.
“In a separate study, researchers said they had found that a particular genetic signature in the tumor can help predict which patients could benefit from the immune-boosting drugs.
“The finding could potentially extend use of these drugs to some patients with colorectal cancer, prostate cancer and other tumors that have seemed almost impervious to the new drugs. Most of the substantial results so far with these expensive drugs have been in treating melanoma and lung cancer.
“ ‘If you have the signature, you should treat with these checkpoint inhibitors,’ Dr. Luis A. Diaz Jr., an associate professor of oncology at Johns Hopkins University and the senior author of the study on the genetic marker, said in an interview, referring to the new drugs.”
It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…