“The addition of ipilimumab to targeted therapy for the treatment of EGFR- and ALK-mutated non-small cell lung cancer demonstrated improved survival despite dose-dependent toxicities, according to results from a phase 1b trial presented at the International Association for the Study of Lung Cancer Multidisciplinary Symposium in Thoracic Oncology.
“Ipilimumab (Yervoy, Bristol-Myers Squibb), a CTLA-4 inhibitor, has demonstrated long-term responses in patients with melanoma; however, the drug is associated with a high rate of grade 3 and grade 4 immune-related adverse events.”
“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.’ ”
“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.”
“Combination treatment with an intratumoral injection of Coxsackievirus A21 (CVA21) and the cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) inhibitor ipilimumab has demonstrated durable response with minimal toxicity among patients with advanced melanoma, according to data (abstract CT114) presented at the American Association for Cancer Research (AACR) Annual Meeting 2017, held April 1–5 in Washington, DC.
“Response to the combination occurred even among several patients whose melanoma had progressed despite prior treatment with an immune checkpoint inhibitor.”
“Bristol-Myers Squibb (BMS) and AstraZeneca have each announced separate delays in the development of PD-1 and CTLA-4 inhibitor combinations as first-line therapies for patients with advanced or metastatic non–small cell lung cancer (NSCLC), according to statements from each of the companies.
“In its statement, BMS noted that it would not be pursuing an accelerated approval for the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) as a frontline therapy for NSCLC. Instead, the company plans to delay the submission of data to the FDA until findings from a phase III study are available, most likely from the phase III CheckMate-227 trial.”
“With the development of novel targeted and immunotherapeutic agents that are more efficacious than traditional chemotherapy, treatment paradigms in melanoma have undergone major changes. Current recommendations for first-line systemic therapy for patients with advanced or metastatic melanoma consider BRAF mutation status, tumor growth rate, and the presence or absence of cancer-related symptoms.
“Immunotherapies with agents that block CTLA-4 or PD-1/PD-L1 checkpoints have been associated with durable responses in a subset of patients, and are often considered for patients with low-volume, asymptomatic metastatic melanoma. Targeted therapies, on the other side, are preferred for patients with BRAF-mutant tumors who have symptomatic disease and benefit from the rapid response associated with these agents.”
Do you have questions about this story? Let us know in a comment below. If you’re wondering whether this story applies to your own cancer case or a loved one’s, we invite you to use our Ask Cancer Commons service.
“Two immuno-oncology drugs in development at AstraZeneca (AZ) have shown potential as a dual therapy for non-small cell lung cancer, according to a new study.
“The phase II trial – reported in Lancet Oncology – found that combining anti-PD-L1 antibody durvalumab with anti-CTLA-4 antibody tremelimumab achieved an overall response rate (ORR) of 23%, significantly higher than has previously been seen with durvalumab alone in this setting.
“The trial was small and focused primarily on safety, but the preliminary efficacy signal – albeit in just 26 patients – is encouraging, according to an editorial accompanying the study by Edward Garon of the David Geffen School of Medicine at the University of California, Los Angeles.”
“A combination of the anti–PD-L1 immune checkpoint inhibitor durvalumab (MEDI4736) with the anti–CTLA-4 monoclonal antibody tremelimumab showed improved tumor response in patients with advanced non–small cell lung cancer (NSCLC) over single-agent therapy.
“The study, published in the Journal for ImmunoTherapy of Cancer, was a phase I, open-label, dose-escalation/expansion study that contained 84 patients. Of these patients, 48 had two or more prior lines of therapy. Data from the study showed improved tumor response regardless of PD-L1 status, with an overall response rate of 25% and 35% of PD-L1-negative patients receiving a response (0% tumor cell staining).”
“The combination of ipilimumab and palliative radiation therapy reduced tumor growth and the spread of metastases in some patients with metastatic melanoma, according to prospective, phase 2 study results presented at the ASTRO Annual Meeting.
“Local radiation therapy has the potential to augment the induction of systemic anti-melanoma immune responses when used in combination with systemic anti–CTLA-4 immunotherapy, according to study background.
“Thus, Susan M. Hiniker, MD, instructor in the department of radiation oncology at Stanford University School of Medicine, and colleagues assessed the safety and efficacy of combining ipilimumab (Yervoy, Bristol-Myers Squibb) with palliative radiotherapy in patients with stage IV melanoma. Researchers also assessed the induction of anti-melanoma immune response.
“The analysis included data from 20 patients (men, n = 14) aged 18 to 83 years who had stage IV melanoma. Patients received palliative radiotherapy and 3 mg/kg IV ipilimumab every 3 weeks for four treatment cycles. The radiotherapy was initiated within 5 days of the first ipilimumab treatment at one or two melanoma sites.”