“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).”
“Immune checkpoint inhibitors have demonstrated encouraging results for patients with small cell lung cancer (SCLC) and mesothelioma, two aggressive thoracic malignancies with few options, according to a presentation by M. Catherine Pietanza, MD, at the 10th Annual New York Lung Cancer Symposium.
“ ‘The antibodies to CTLA-4, PD-1, and PD-L1 can be safely given to these patients. Responses are seen and are durable. There is a benefit in both platinum-sensitive and platinum-refractory SCLC,’ said Pietanza, a medical oncologist at Memorial Sloan Kettering Cancer Center.
“Chemotherapy has traditionally been the treatment of choice for most patients with SCLC and mesothelioma beyond the frontline setting. However, outcomes are poor with these therapies, specifically for SCLC, where the median survival following second-line therapy ranges from 6 to 9 months.”
“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.”
“Patients with advanced melanoma skin cancer survive for longer without their disease progressing if they have been treated with a combination of two drugs, nivolumab and ipilimumab, than with either of these drugs alone. New results show that these patients also do better regardless of their age, stage of disease and whether or not they have a cancer-driving mutation in the BRAF gene.
“Dr James Larkin, a Consultant Medical Oncologist at The Royal Marsden, London, UK, told the 2015 European Cancer Congress, that results from the CheckMate 067 phase III clinical trial had already shown that the combination of the two drugs, which target two different pathways that regulate the immune system, improved the progression-free survival in patients with melanoma who had not received any other treatment. However, until now it was not known whether this remained the case when the results were analysed according to genetic status, age and how advanced was their disease.
“Nivolumab is an inhibitor of the programmed cell death protein 1 (known as PD-1), which functions as an immune checkpoint, playing an important role in the immune system. Ipilimumab inhibits the CTLA-4 checkpoint, which also plays a role in the immune system.”
“Adverse events related to immune activation with ipilimumab (Yervoy, Bristol-Myers Squibb Company) may be higher than clinical trials have previously suggested, according to a study of real-world clinical data from patients treated at Memorial Sloan Kettering Cancer Center, in New York City. The study was published online August 17 in the Journal of Clinical Oncology.
“Ipilimumab was the first of the novel immunotherapies launched for melanoma, and so far it is the only one that is an anticytotoxic T-cell lymphocyte-4 (anti-CTLA-4) antibody. It can cause immune activation and adverse reactions, such as diarrhea, rash, hepatitis, and pituitary inflammation. These reactions are often treated with steroids; severe reactions may require treatment with an anti–tumor necrosis factor alpha (anti-tNFα), such as infliximab (Remicade, Janssen Biotech, Inc).
” ‘Among our small group of physicians highly experienced with ipilimumab, we felt that 35% of the patients required systemic steroids to treat adverse events,’ commented lead author Paul Chapman, MD, a specialist in metastatic melanoma at Memorial Sloan Kettering Cancer Center.”
Of all cancer types, melanoma is the most investigated in terms of its potential to be treated through immune system-based approaches. More immunotherapy drugs are approved for melanoma than for any other type of cancer, and more are in development. Recent additions to the immunotherapy arsenal are the ‘anti-PD-1’ immune checkpoint blockade drugs pembrolizumab (Keytruda) and nivolumab (Opdivo). Continue reading…
“AstraZeneca AZN, -0.75% and MedImmune, AstraZeneca’s global biologics research and development arm, today presented encouraging results from their novel combination-focused immuno-oncology portfolio at the American Society of Clinical Oncology (ASCO) Annual Meeting 2015.
“Overall, data indicated clinical activity with manageable safety profiles for the anti-programmed cell death ligand 1 (PD-L1) monoclonal antibody MEDI4736, both as monotherapy and in combination with other immuno-oncology and small molecule therapies across different tumor types and tumor biology.
“MEDI4736 and tremelimumab combination shows clinical activity and tolerability in both PD-L1 positive and PD-L1 negative advanced non-small cell lung cancer (NSCLC) patients; dose confirmed for future studies
“Results from the combination study of MEDI4736 and tremelimumab, a cytotoxic T-lymphocyte-associated protein-4 (CTLA-4) monoclonal antibody, in the treatment of advanced NSCLC, demonstrated clinical activity in heavily-pretreated patients with a manageable safety profile, establishing appropriate doses to move forward into Phase III combination trials.”
“Melanoma is predicted to result in approximately 10,000 deaths in 2015. The majority of these deaths are due to advanced stage disease that has spread or metastasized to other sites. The prognosis for patients with metastatic melanoma remains poor, with 5-year survival rates of 63 percent in patients who have metastatic disease in regional lymph nodes, and only 17 percent in patients who have metastatic disease in distant sites. Moffitt Cancer Center researchers participated in an international phase 3 study that demonstrated that a drug called ipilimumab improves the relapse-free survival of advanced stage melanoma patients rendered free of disease surgically but at high risk for relapse.
“Ipilimumab is approved for the treatment of melanoma that cannot be surgically removed or that has metastasized to different sites. Ipilimumab targets a protein called cytotoxic T lymphocytic antigen-4 (CTLA-4) that is found on a type of immune cell called a T cell. CTLA-4 keeps the immune system in check to avoid autoimmune disease by downregulating T cell activity. Tumors take advantage of CTLA-4 activity to avoid immune detection. By targeting CTLA-4, ipilimumab restimulates the immune system to target tumor cells.
“Researchers wanted to determine if ipilimumab could improve the survival of advanced-stage melanoma patients if it was given after the surgical removal of both their primary melanoma tumors and their regional lymph nodes.”
It has become routine practice to prescribe targeted drugs to patients with metastatic non-small cell lung cancer (NSCLC), whose tumors harbor molecular alterations in EGFR, ALK, and ROS. However, the majority of patients with NSCLC have no targetable mutations and lack good treatment options. Enter immunotherapy drugs, specifically ‘immune checkpoint blockade antibodies,’ to which many refer simply as ‘anti-PD-1 drugs,’ or simply ‘PD-1 drugs.’ In this post, I provide some updates on the efficacy of anti-PD-1 and anti-PD-L1 drugs in lung cancer. Continue reading…