“Prostate cancer, notoriously resistant to immunotherapy due to its immunologically cool nature, triggers two pathways to chill an immune attack after one immunotherapy drug fires up the immune system, researchers at The University of Texas MD Anderson Cancer Center report in Nature Medicine.
“Based on their findings, the researchers launched a clinical trial for stage IV prostate cancer in March combining two drugs that target separate brakes on the immune system. The checkpoint inhibitors largely failed individually against the disease. Their results also implicate for the first time on a human tumor a third brake called VISTA in potentially inhibiting immune response.”
“Advancements in immunotherapy in the field of prostate cancer have been slow ever since the FDA approval of sipuleucel-T (Provenge) several years ago.
” ‘It’s an exceptionally challenging area. After the success of sipuleucel-T, there have been combinatorial approaches using radiopharmaceuticals, such as radium-223, the checkpoint inhibitor ipilimumab (Yervoy), as well as some chemotherapy regimens,’ says Susan F. Slovin, MD, PhD.
“In an interview with OncLive at the 2017 Interdisciplinary Prostate Cancer Congress, Slovin, a medical oncologist at Memorial Sloan Kettering Cancer Center, offered her expert insight on the current state of immunotherapy in prostate cancer.”
“Investigators are looking into a novel immunotherapy combination that pairs the first-in-class IDO1 inhibitor epacadostat (INCB024360) with the checkpoint blockade agent pembrolizumab (Keytruda) in patients with unresectable or metastatic melanoma.
“The phase III KEYNOTE-252/ECHO-301 trial, which is enrolling at more than 120 locations, will randomize 600 patients in a 1:1 ratio to either epacadostat combined with pembrolizumab or pembrolizumab plus placebo (NCT02752074).”
“The combination of immunotherapy and chemotherapy is showing promising response rates in certain patients with triple-negative breast cancer (TNBC), said ESO Umberto Veronesi Memorial Award Winner Giuseppe Curigliano, MD, PhD, who addressed genetic determinants of breast cancer immunogenicity in his award lecture at the 15th St. Gallen International Breast Cancer Conference.
“Curigliano emphasized the importance of patient selection in optimizing immunotherapy in breast cancer. In a study done by Curigliano, in collaboration with the Sidra Medical Center in Qatar, a subgroup of patients with TNBC who would derive benefit from checkpoint inhibitors were identified. This group, he stated, should be selected based on individual assessment of tumor-infiltrating lymphocytes.”
“The MEK inhibitor binimetinib improved progression-free survival compared with dacarbazine in patients with NRAS-mutant melanoma, according to the phase III results of the NEMO trial published in Lancet Oncology.
“In addition, improved progression-free survival was seen in patients who had previously failed immunotherapy, the current guideline-recommended first-line treatment.
” ‘Future treatment algorithms for metastatic melanoma might incorporate binimetinib therapy in patients with advanced NRAS-mutant melanoma, including after the failure of immunotherapy,’ wrote Reinhard Dummer, MD, of the department of dermatology at the University Hospital Zurich Skin Cancer Center in Switzerland, and colleagues.”
“An emerging approach for cancer treatment seeks to combine radiation therapy with immune checkpoint inhibitors (ICPIs) to more effectively control tumors in the chest with an acceptable risk of severe treatment-related side effects. Ten percent of patients in a retrospective analysis of metastatic lung cancer experienced severe toxicity as a result of the combination therapy. Findings will be presented tomorrow at the 2017 Multidisciplinary Thoracic Cancers Symposium.”
“Despite breast tumors’ lower mutational loads than lung cancers and melanoma—cancers in which immunotherapy have shown particular promise—breast cancers are nevertheless immunogenic, Elizabeth A. Mittendorf, MD, PhD, of the University of Texas MD Anderson Cancer Center in Houston, reported at the 34th Annual Miami Breast Cancer Conference, held March 9–12 in Miami Beach, Florida.
“Multiple clinical trials are now underway to evaluate immunotherapy strategies in breast cancer, Mittendorf noted.
“Combination immunotherapy regimens are ‘likely the way forward’ and appropriate combinatorial strategies will hinge importantly on disease stage, she said.”
“The FDA granted fast track designation to ImmunoPulse IL-12 for the treatment of metastatic melanoma that progressed during therapy with pembrolizumab or nivolumab.
“ImmunoPulse IL-12 (OncoSec Medical) is an intratumoral anticancer gene therapy that expresses interleukin-12 (IL-12).
“ ‘With the number of melanoma patients now being treated with either pembrolizumab (Keytruda, Merck) or nivolumab (Opdivo, Bristol Myers Squibb) in either the first- or second-line settings, there will be an increasing number of patients who will not respond to therapy,’ Punit Dhillon, president and CEO of OncoSec, said in a company-issued press release. ‘Thus, there is a clear need for treatments that can rescue these patients and help them benefit from these immunotherapies.’ ”