A Subset of Patients with Metastatic Melanoma Achieves Clinical Benefit from Combination of Immunotherapy and Radiation Therapy

“Immunotherapy combined with palliative radiation therapy (RT) for a subset of patients with metastatic melanoma reduces the growth and spread of the cancer, according to research presented today at the American Society for Radiation Oncology’s (ASTRO’s) 57th Annual Meeting.

“Although melanoma is not the most common type of skin cancer, it is the most serious type. Stage IV melanoma indicates that the cancer has metastasized and spread through lymph nodes to distant sites in the body and/or to the body’s organs. The liver, lungs, bones and brain are areas most frequently affected by these metastatic lesions. Immunotherapy—the use of medicines to stimulate a patient’s own immune system to recognize and destroy cancer cells more effectively—can be combined with other cancer therapies to aid in the treatment of stage IV melanoma. Ipilimumab is an immunotherapy approved for use in melanoma patients.

“This phase II clinical trial is one of the first prospective clinical trials to report results from the treatment of metastatic melanoma with the combination of RT and systemic immunotherapy. In this study, 20 patients with stage IV melanoma were treated with palliative RT and intravenous ipilimumab (3mg/kg) every three weeks, for a total of four treatment cycles. RT was initiated to one or two sites of metastatic melanoma within five days of the initial immunotherapy treatment. All patients had at least one nonirradiated (untreated) site of metastasis that could be used for assessment of response to therapy.”


Video: Dr. Kunz on Potential of Immunotherapy in Neuroendocrine Tumors

“Pamela L. Kunz, MD, assistant professor of Medicine (Oncology), Stanford University School of Medicine, discusses the potential of immunotherapy in the treatment of patients with neuroendocrine tumors (NETs).

“There are currently some clinical trials under development looking at immunotherapy in NETs both at Stanford University School of Medicine and University of Pennsylvania, Kunz explains. One phase I/II trial will examine the safety and efficacy of intratumoral injection of ipilimumab combined with an anti—PD-L1 agent in these patients.”

“It is possible that immunotherapy agents could be agnostic to disease sites, Kunz says. Though it was originally believed that PD-1/PD-L1 expression is a requirement to be a predictive biomarker, additional research could show that it may not be necessary.”

Click through to watch the video.


Surgery on Melanoma That Has Spread into Abdomen More than Doubles Patient Survival Time

“Patients with metastatic melanoma who undergo surgery to remove lesions that have spread into the abdomen live more than twice as long as those treated with drug therapy alone, according to novel new research by a North Shore-LIJ Health System cancer surgeon.

“The study, by North Shore-LIJ surgical oncologist Gary B. Deutsch, M.D., M.P.H., will be presented on Oct. 8 at the 2015 Clinical Congress of the American College of Surgeons in Chicago. Dr. Deutsch’s research is the first comprehensive look at the survival benefits of surgical resection for melanoma metastases in the abdomen since the advent of groundbreaking immunotherapies in recent years that stimulate patients’ immune systems to destroy cancer cells, improving once-dismal survival rates.

“Dr. Deutsch’s study could immediately impact how oncologists across the United States approach metastatic melanoma cases in which the cancer has spread to abdominal organs, he said.”


Dr. David Ettinger Discusses the Road Ahead for Immunotherapy in NSCLC

“Immunotherapy options are expanding in the field of non–small cell lung cancer (NSCLC), with the recent FDA approval of pembrolizumab (Keytruda) for patients with pretreated advanced NSCLC across all histologies whose tumors express PD-L1.

“Pembrolizumab is the second PD-1 inhibitor approved for treatment of this disease. The approval was based on findings from the phase I KEYNOTE-001 trial. In this study, a subgroup of patients treated with pembrolizumab had an overall response rate (ORR) of 41%. In the entire study population, the ORR was nearly 20%.

“The anti–PD-1 agent nivolumab (Opdivo) was previously approved by the FDA in March 2015 for patients with squamous NSCLC who have progressed on or after platinum-based chemotherapy. Nivolumab also recently received an FDA priority review designation in the nonsquamous NSCLC setting, with a decision deadline of January 2, 2016.”


Investigational KW-0761 Efficiently Depletes Immune System-Suppressing Treg Cells

“Main Finding(s): In a phase Ia clinical trial, immune cells called Tregs, which can inhibit anticancer immune responses, were efficiently eliminated from the blood of patients with lung or esophageal cancer by treatment with the investigational therapeutic antibody KW-0761…

“Background: Tregs, which are characterized by expression of the proteins FoxP3 and CD4, have several important roles in the  system, one of which is to prevent the immune system from attacking the body and causing autoimmune diseases. However, they also suppress the  against , Ueda explained, leading to the hypothesis that depleting Tregs in with cancer may augment the natural anticancer immune response.”


Nivolumab/Ipilimumab Combination FDA Approved for BRAF Wild-Type Melanoma

“The combination of nivolumab and ipilimumab has received accelerated FDA approval as a treatment for patients with BRAF V600 wild-type (WT) unresectable or metastatic melanoma, based on findings from the phase II CheckMate-069 study.

” ‘Historically, metastatic melanoma has been a difficult disease to treat. Now, a new treatment option based on the combination of two valued immuno-oncology agents demonstrates significant efficacy versus ipilimumab in metastatic melanoma,’ said Jedd D. Wolchok, MD, PhD, chief, Melanoma and Immunotherapeutics Service, Department of Medicine and Ludwig Center at Memorial Sloan Kettering Cancer Center, in a statement. ‘Today’s approval represents a step forward for the melanoma community, providing hope for patients with metastatic melanoma.’ ”


Frequency of Certain Immune Cells in Blood May Predict Metastatic Melanoma Response to Pembrolizumab

“Among patients with metastatic melanoma treated with the immunotherapy drug pembrolizumab (Keytruda), those whose cancer responded to the treatment had a higher frequency of immune cells called T cells that were positive for the proteins CD8, PD-1, and Bim (CD8+PD-1+Bim+ T cells) in blood samples taken immediately before starting pembrolizumab than those who had disease progression, according to data presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference, held Sept. 16–19.

“Pembrolizumab, which targets the protein PD-1, was approved by the U.S. Food and Drug Administration for treating metastatic melanoma in September 2014. Some patients with metastatic melanoma have remarkable responses to pembrolizumab, whereas others do not respond at all, according to Roxana S. Dronca, MD, a medical oncology consultant and assistant professor of oncology at the Mayo Clinic in Rochester, Minnesota.”


Immune System–Boosting Agent May Reduce Early-Stage Melanoma Recurrences

“Among patients with clinically stage I or stage II melanoma, those treated with the immune system–boosting agent CpG-B were less likely to experience recurrence of their disease than those who received placebo, according to results from two randomized, placebo-controlled phase II clinical trials presented at the CRI-CIMT-EATI-AACR International Cancer Immunotherapy Conference (Abstract A050), held September 16–19 in New York.

“ ‘Even though stage 1 and stage 2 melanomas can be removed surgically, in a considerable proportion of patients, cells from the tumor have already spread and eventually lead to tumor recurrence,’ said Tanja D. de Gruijl, PhD, Professor and Head of the Immunotherapy Laboratory in the Department of Medical Oncology at the VU University Medical Center Cancer Center Amsterdam. ‘We set out to investigate whether intradermal injection of the immune-stimulatory compound CpG-B around the site of surgical removal of the primary tumor could boost patients’ antimelanoma immune responses and provide local and systemic protection against early metastatic events that could otherwise lead to tumor recurrence.’ “


To PD-L1 or Not to PD-L1: That Is the Question


These days, it seems that I write mostly about immune checkpoint blockade drugs, or some other new immunotherapy treatment for cancer. This post is no different—it covers PD-L1, a protein that is at the center of clinical decisions for selecting patients who are likely to benefit from treatment with an anti-PD-1 or anti-PD-L1 drug. Continue reading…