Ipilimumab Confers Long-Term Survival in Advanced Melanoma

“Ipilimumab was associated with long-term OS rates that plateaued after 3 years in patients with unresectable or metastatic melanoma, according to results from a pooled analysis of phase 2 and phase 3 trials.

“ ‘We observed an apparent plateau in the survival curve regardless of prior therapy, ipilimumab dose or treatment regimen,’ Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen, Germany, and colleagues wrote. ‘In all analyses, including those with OS data from patients in the expanded access treatment protocol, the survival curves seemed to consistently begin around year 3 and extended up to 10 years in some patients.’

“Schadendorf and colleagues sought to provide an estimate of the long-term OS benefit associated with ipilimumab (Yervoy, Bristol-Myers Squibb), which was approved in 2011 for the treatment of unresectable or metastatic melanoma.

“Researchers evaluated data from 1,861 patients with advanced melanoma who were enrolled in 10 prospective and two retrospective clinical trials. Approximately two-thirds (n = 1,257) of the patients had received prior treatment.”


Keytruda Performs Much Better than Yervoy in a Phase III Trial

“Merck (NYSE:MRK), known as MSD outside the United States and Canada, today announced that the randomized, pivotal Phase 3 study (KEYNOTE-006) investigating KEYTRUDA® (pembrolizumab) compared to ipilimumab in the first-line treatment of patients with advanced melanoma has met its two primary endpoints of progression-free survival and overall survival. The trial will be stopped early based on the recommendation of the study’s independent Data Monitoring Committee. In KEYNOTE-006, KEYTRUDA demonstrated a statistically significant and clinically meaningful improvement in overall survival and progression-free survival compared to ipilimumab. The safety profile of KEYTRUDA in this trial was similar to the safety profile previously reported in advanced melanoma. KEYTRUDA is the first anti-PD-1 therapy to demonstrate a survival advantage compared to the standard of care for the first-line treatment of advanced melanoma. These data will be presented in the opening plenary session at the American Association of Cancer Research (AACR) Annual Meeting in Philadelphia, April 18-22.

” ‘Evidence from our clinical program for KEYTRUDA will help to define the appropriate treatment of advanced melanoma,’ said Dr. Roger Perlmutter, president, Merck Research Laboratories. ‘We greatly appreciate the efforts of our investigators and their patients in this important study, and we look forward to the presentation of overall survival data from KEYNOTE-006 at the AACR annual meeting.’ “


Nivolumab Works in Melanoma Patients for Whom Previous Treatments Did Not

“More patients with advanced melanoma who had progressed on ipilimumab with or without a BRAF inhibitor were able to achieve an objective response when treated with the PD-1 immune checkpoint inhibitor nivolumab than with alternative chemotherapy options, according to the interim analysis results of the CheckMate 037 trial published recently in Lancet Oncology.

“In fact, the rate of objective response was about threefold greater with nivolumab compared with investigator’s choice of chemotherapy; however, no difference in progression-free survival in the intention-to-treat population was noted.

“These results were the basis of the December 2014 US Food and Drug Administration accelerated approval of nivolumab for this patient population.

“ ‘Findings from our study show that nivolumab leads to clinically meaningful improvements in the proportion of patients achieving an objective response and provide a manageable safety profile when compared with chemotherapy,’ wrote Jeffrey S. Weber, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues. ‘Nivolumab can now be considered as a new treatment option for patients that have progressed after ipilimumab, or a BRAF inhibitor and ipilimumab if their melanoma is BRAF V600–mutated.’ ”


Triple Combo: Two Targeted Drugs Plus Immunotherapy Show Promise in BRAF-Mutant Melanoma

“Results of a new study by UCLA researchers has found that a groundbreaking new triple combination therapy shows promising signs of more effectively controlling advanced melanoma than previous BRAF + MEK inhibitor or BRAF inhibitor + immunotherapy combos alone, and with increased immune response and fewer side effects.

“An estimated 70,000 new cases of metastatic melanoma are diagnosed each year in the United States, and of those 8,000 will die of the disease. About 50 percent of these men and women (or 35,000 a year) have a mutated protein called a BRAF mutation, which in most cases allows melanoma to eventually build up a resistance to many drug therapies.

“In the new study led by UCLA Jonsson Comprehensive Cancer Center member Dr. Antoni Ribas and colleague Dr. Siwen Hu-Lieskovan, UCLA scientists combined targeted therapies utilizing a BRAF inhibitor (dabrafenib) and MEK inhibitor (trametinib) with immunotherapy. The three together are shown to be more effective treatments by sensitizing the patients’ own immune system to enhance immunotherapy, and reduce the probability of the melanoma eventually developing resistance.

“This is a significant advance compared to previous drug combination findings, in which a combined BRAF inhibitor (vemurafenib) with immunotherapy (ipilimumab) caused serious liver toxicity in some patients, and the targeted therapies (BRAF and/or MEK inhibitors) became less effective and reactivated cancer cell growth.”


Combining Radiation and Immune Therapies Could Be a Good Option for Melanoma Treatment

“Treating metastatic melanoma with a triple threat—including radiation therapy and two immunotherapies that target the CTLA4 and PD-1 pathways—could elicit an optimal response in more patients, one that will boost the immune system’s attack on the disease, suggests a new study from a multidisciplinary team of researchers from Penn’s Abramson Cancer Center published today in Nature.

“The study, led by senior authors Andy J. Minn, MD, PhD, assistant professor of Radiation Oncology, Robert Vonderheide, MD, DPhil, the Hanna Wise Professor in Cancer Research, Amit Maity, MD, PhD, professor of Radiation Oncology, and E. John Wherry, PhD, professor of Microbiology and director of the Institute for Immunology at the Perelman School of Medicine at the University of Pennsylvania, reports for the first time on the response and resistance to radiation combined with ipilimumab (an antibody against CTLA4) in both patients and mice.

“In the phase I clinical study, known as the ‘RadVax’ trial, the team found that combining ipilimumab with radiation was safe and shrank tumors in a subset of 22 metastatic melanoma patients (18 percent). The concurrent mouse study shed light on a mechanism of resistance, known as the PD-L1 pathway, found in many patients whose cancers progressed, suggesting that an antibody against PD-L1 or its partner PD-1 is an ideal third treatment to improve response and immunity.”


Ipilimumab Is on the Way to Approval for Stage III Melanoma Treatment

“The FDA has accepted a supplemental Biologics License Application (sBLA) for ipilimumab (Yervoy) as an adjuvant treatment of patients with stage III melanoma at high risk of recurrence following complete resection, according to Bristol-Myers Squibb, the company developing the drug. The FDA is scheduled to make a decision on adjuvant ipilimumab by October 28, 2015.

“The acceptance of the sBLA is based on results from the phase III EORTC 18071 trial, which was presented at the 2014 ASCO Annual Meeting. This study showed a 25% improvement in recurrence-free survival (RFS) in patients treated with ipilimumab versus placebo (HR = 0.75; 95% CI, 0.64–0.90).

“ ‘This is a promising treatment—we saw substantially fewer recurrences among patients who are at high risk of relapse,’ Alexander Eggermont, MD, PhD, director general of the Gustave Roussy Cancer Campus Grand Paris in France, said in an 2014 ASCO Annual Meeting press release. ‘We’ve seen many impressive new treatments for advanced melanoma in recent years. This trial with ipilimumab is the first to show we may be able to give these new drugs earlier in the course of disease, where they can do more good and potentially cure more patients.’ ”


Study Confirms Long-Term Benefits of Melanoma Immunotherapy

“A long-term follow up of people on an international clinical trial has confirmed the benefit of immunotherapy for certain patients with advanced (stage 3 or 4) melanoma.

“More than 18 per cent of patients were still alive five years after being treated with ipilimumab (Yervoy) in combination with a chemotherapy drug called dacarbazine.

“This compared to fewer than nine per cent who were treated with chemo alone.

“Ipilimumab is one of a new class of cancer treatments that target the immune system, and works by homing in on a molecule found on immune cells called CTLA-4. This relieves the molecular ‘brakes’ on a patient’s immune system, allowing it to attack their cancer.

“The study, which began recruiting patients 2006 – including several from the UK – also confirmed low rates of serious side-effects among patients who took the drug long-term.”


Bavarian Nordic Vaccine Helps Prolong Life in Prostate Cancer Trial

“An experimental therapeutic vaccine from Danish drugmaker Bavarian Nordic helped significantly extend survival in patients with advanced prostate cancer, according to results of a small early-stage trial conducted by the U.S. National Cancer Institute.

“Shares of Bavarian Nordic closed up almost 12 percent in Copenhagen after the company released the data on Tuesday.

“The study involved 30 patients with prostate cancer that had failed to benefit from standard treatments that reduce levels of testosterone, the male hormone that fuels the cancer.

“Patients were treated with the company’s Prostvac vaccine, in addition to escalating doses of Bristol-Myers Squibb Co’s Yervoy, an approved injectable treatment for advanced melanoma that works by taking the brakes off the body’s immune system.”


Drug Combo Shows Promise for Treating Metastatic Melanoma

The gist: In a clinical trial, a treatment that combines the drugs ipilimumab (Yervoy) and fotemustine showed promise for treating patients with metastatic melanoma.

“The combination of ipilimumab and fotemustine demonstrated long-term efficacy in patients with metastatic melanoma, according to extended follow-up results of a phase 2 study.

“The NIBIT-M1 study evaluated the combination of ipilimumab (Yervoy, Bristol-Myers Squibb) and fotemustine as first- or second-line treatment for patients with metastatic melanoma.

“Initial results suggested promising activity of the combination in this population, including those with or without brain metastases.

“For the current analysis, Anna Maria Di Giacomo, MD, of the department of medical oncology and immunotherapy at the University Hospital of Siena, Italy, and colleagues assessed 3-year outcomes.”