Author Interviews, Cancer Research, Lancet, Nature / 19.05.2020

MedicalResearch.com Interview with: Matthew Galsky, MD Icahn School of Medicine at Mount Sinai New York, NY MedicalResearch.com: What is the background for this study? Response: Standard first-line treatment for metastatic urothelial (bladder) cancer has been platinum-based chemotherapy for decades. In 2016, atezolizumab, an immunotherapy that inhibits PD-L1, received accelerated approval by the FDA for the treatment of metastatic urothelial cancer for patients progressing despite prior platinum-based chemotherapy and this was followed by approvals for 4 additional PD-1 or PD-L1 inhibitors in this setting over the next couple years. With this first new drug class approved, representing the first new drugs approved for metastatic urothelial cancer for decades, logical question arose (a) should we combine these drugs with platinum-based chemotherapy in the first-line metastatic treatment setting and (b) is there a role to replace first-line chemotherapy with atezolizumab monotherapy. The IMvigor 130 trial was designed to address these questions. The trial enrolled 1213 patients who were randomized to treatment with (a) atezolizumab plus platinum-based chemotherapy, (b) placebo + platinum-based chemotherapy, or (c) atezolizumab monotherapy. The trial employed a hierarchical analysis plan such that comparisons between arms for certain endpoints could only be formally tested if other the preceding comparisons demonstrated a significant improvement.  (more…)
Allergies, Author Interviews, Cancer Research, Immunotherapy / 07.06.2019

MedicalResearch.com Interview with: Prof. Olivier Lambotte, MD, PHD Professor of Internal Medicine Paris XI University Medical School Research Director Control of Chronic Viral Infections DepartmentProf. Olivier Lambotte, MD, PHD Professor of Internal Medicine Paris XI University Medical School Research Director Control of Chronic Viral Infections Department MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Immune checkpoint inhibitors (ICIs) anti-programmed death-1 (PD-1) or anti-programmed death ligand-1 (PD-L1) have proven efficacy in the treatment of many cancers but patients may experience immune-related adverse events (irAEs). Immune checkpoint inhibitors is usually stopped when grade 2 or higher irAE occur. Data are very limited  on the safety of resuming treatment after such an event. We  studied all adult patients referred to the ImmunoTOX toxicity review board at the Gustave Roussy cancer center (Villejuif, France) in 2015-2017 with  irAE grade 2 or higher for whom the  rechallenge was questioned. Among 93 patients with a broad spectrum of cancers, 40 patients (43%) were rechallenged with the same anti-PD-1 or anti-PD-L1. The rechallenged and non-rechallenged groups did not differ in terms of age, time to initial irAE, irAE severity, or steroid use. With a median follow-up period of 14 months, the same irAE or a different irAE occurred in 22 patients (55%). The second irAEs were not more severe than the first. Earlier initial toxicity was associated with more frequent irAE recurrence. (more…)
Author Interviews, Cancer Research, JAMA, Yale / 15.05.2018

MedicalResearch.com Interview with: Jeremy O'Connor, MD Section of General Internal Medicine Department of Internal Medicine Postdoctoral Fellow, National Clinician Scholars Program Yale University MedicalResearch.com: What is the background for this study?   Response: There has been a lot of enthusiasm for the use of novel therapies in cancer care, and in particular for novel anticancer agents known as immune checkpoint inhibitors. But very little is known about how quickly providers have adopted immune checkpoint inhibitors into clinical practice. Existing studies suggest, in fact, that the process of clinical adoption is slow, with conventional wisdom holding that it takes an average of 17 years for new evidence to change practice. Our study evaluated whether the adoption of novel therapies might be much faster in certain contexts with the early use of immune checkpoint inhibitors as a notable example. (more…)
Author Interviews, Cancer Research, JAMA, Lung Cancer, Radiation Therapy / 02.10.2017

MedicalResearch.com Interview with: Florence K Keane MD Resident, Radiation Oncology Harvard Radiation Oncology Program Boston, Massachusetts MedicalResearch.com: What is the background for this study? Response: Checkpoint inhibitors (CPIs) have recently transformed the management of patients with metastatic lung cancer, demonstrating significant improvements in overall and progression-free survival in both the first-line setting in patients with increased expression of PD-L1 (≥50%) and in patients with previously treated NSCLC who have progressed on chemotherapy. CPIs are also moving into the treatment of patients with localized lung cancer, with the recently published PACIFIC trial demonstrating a significant improvement in progression-free survival in patients with inoperable stage III NSCLC treated with adjuvant durvalumab after definitive chemoradiotherapy. However, CPIs are associated with unique toxicities as compared to cytotoxic chemotherapy, including pulmonary, endocrine, neurologic, gastrointestinal, and dermatologic adverse events, which may be fatal in some cases. The risk of autoimmune pneumonitis with checkpoint inhibitors is estimated to be on the order of 5%. Many patients with lung cancer will require radiotherapy for palliation of symptoms. Thoracic radiotherapy (TRT) is also a risk factor for pneumonitis, with a dose- and volume-dependent impact on risk. However, it is unknown whether treatment with CPIs and TRT is associated with increased risk of toxicity. (more…)