“Immunotherapy has led a transformation for melanoma care but combinations of anti–PD-1 and CTLA-4 agents are toxic and biomarkers are not available to help personalized treatment, calling for further research into less toxic and more effective options, according to a presentation by Caroline Robert, MD, PhD, at the 2017 World Congress of Melanoma.
“At this point, the only approved immunotherapy combination remains the PD-1 inhibitor nivolumab (Opdivo) and the CTLA-4 inhibitor ipilimumab (Yervoy). However, research into combination approaches is now focusing on triplets of anti–PD-1 therapies and new checkpoints, such as IDO. Additionally, ongoing research continues to search of a biomarker of response for immunotherapy in melanoma.”
“Patients with unresectable, or inoperable, lung cancer are often given a dismal prognosis, with low rates of survival beyond a few years. Researchers exploring combination therapies have recently discovered improved survival rates by up to one year when patients treated with a newly formulated chemotherapy regimen are also given radiation therapy.
“A group of patients with metastatic non-small-cell lung cancer (mNSCLC) who had already been enrolled in a clinical trial were given radiation therapy, in addition to their treatment with a novel chemotherapy formulation, mPEBev, which was designed for its immune-modulating and anti-angiogenic effects. The mPEBev regimen is composed of fractionated cisplatin, oral etoposide, and bevacizumab, a monoclonal antibody that inhibits blood vessel growth in the tumor. Treatments were administered metronomically, spaced out in the safest possible doses to reduce side-effects and toxicity.”
“Whether a melanoma patient will better respond to a single immunotherapy drug or two in combination depends on the abundance of certain white blood cells within their tumors, according to a new study conducted by UC San Francisco researchers joined by physicians from UCSF Health. The findings provide a novel predictive biomarker to identify patients who are most likely to respond well to a combination of immunotherapy drugs known as checkpoint inhibitors—and to protect those who won’t respond from potentially adverse side effects of combination treatment.
” ‘Combination immunotherapy is super-expensive and very toxic,’ said Adil Daud, MD, director of Melanoma Clinical Research at the UCSF Helen Diller Family Comprehensive Cancer Center and senior author of the new study. ‘You’re putting patients at a lot of extra risk if they don’t need it, and you can adjust for that risk by knowing in advance who can benefit.’ ”
There are many hopes that combining immune checkpoint inhibitor drugs, or combining them with drugs of other types (immunotherapy, targeted therapy, or chemotherapy) is the future of treatment for many kinds of cancer. Literally hundreds of clinical trials are actively exploring these combinations, and melanoma is the cancer for which trials of this type abound. Last month, the annual meeting of the American Society of Clinical Oncology (ASCO) in Chicago featured just a few presentations in this area, apparently because it is too early to report results from the many ongoing trials with drug combinations. Continue reading…
“Eli Lilly and Company (NYSE: LLY) today announced that results from the Phase 3 MONARCH 2 study showed that abemaciclib, a cyclin-dependent kinase (CDK)4 & 6 inhibitor, in combination with fulvestrant, significantly improved progression-free survival (PFS) compared to treatment with fulvestrant alone in women with hormone-receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2-), advanced breast cancer who have relapsed or progressed after endocrine therapy (median PFS, 16.4 vs. 9.3 months, respectively, HR: 0.553; 95% CI: 0.449, 0.681, P < .0000001). The data were presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting (Abstract #1000) and simultaneously published online in the Journal of Clinical Oncology.”
“The Wall Street gang attending the American Society of Clinical Oncology (ASCO) annual meeting here will be crowding around a scientific poster this morning, craning their necks to see updated results from a small clinical trial combining Incyte’s (INCY) IDO inhibitor epacadostat with Merck’s (MRK) checkpoint inhibitor Keytruda in patients with non-small cell lung cancer.
“The headline number: The overall response rate remains 35%, although two lung cancer patients now have improved to complete responses, another 12 patients have a partial response. The data are updated as of Feb. 27.”
“Nivolumab plus ipilimumab demonstrated an intracranial response (ICR) rate of 42% in asymptomatic patients with melanoma brain metastases who had not received prior local therapy to the brain.
“In the phase II Anti-PD1 Brain Collaboration (ABC) trial, the 6-month intracranial PFS rate was 46% with the anti–PD-1/CTLA-4 combination.
” ‘The combination of nivolumab and ipilimumab has high activity in melanoma brain metastases and may be considered for upfront therapy in such patients,’ said lead author Georgina V. Long, BSc, PhD, MBBS, clinical researcher at the Melanoma Institute Australia and Westmead Hospital in Sydney.”
“High response rates to a pair of combination therapies point to potentially new options for a group of metastatic melanoma patients who have been largely left out of recent treatment progress – those whose disease has spread to the brain.
“A combination regimen of two immunotherapies and another of two targeted therapies each significantly shrank metastatic brain tumors in at least 50 percent of patients in separate multi-center clinical trials presented today at the 2017 ASCO Annual Meeting by principal investigators from The University of Texas MD Anderson Cancer Center.”
“Immunotherapy agents, both as monotherapy and in combination, are emerging in the pipeline of non–small cell lung cancer (NSCLC) and could end up competing as frontline treatment for patients, explains Sukhmani Padda, MD.
“For example, the PD-1 inhibitor pembrolizumab (Keytruda) is the sole immunotherapy agent approved in the first-line setting for patients with NSCLC; however, many other immunotherapy agents and combination regimens are in development that are aimed at this line of therapy.”