“In a new study by Yale Cancer Center, scientists suggest that as the number of clinical trials in cancer immunotherapy grows exponentially, some caution should be exercised as we continue to better understand the biology of these new therapeutic targets. The findings are published today in the journal Cell.
“Researchers around the world have been racing to create therapies that unleash the power of our immune systems against cancer. The most successful of these immunotherapies, which target a molecular pathway known as PD-1/PD-L1, have brightened the landscape for many people suffering with lung cancer and other types of tumors.”
“ASCO and Friends of Cancer Research (Friends) applaud the National Cancer Institute’s (NCI) recent revision of its clinical trial protocol template to broaden eligibility criteria for cancer clinical trials. The protocol template was expanded to help increase the opportunity for participation in NCI-funded clinical trials for patients with certain health-care conditions, as well as to provide an opportunity for patients younger than age 18 to participate in adult clinical trials in certain circumstances.”
Immunotherapy includes a number of strategies that harness the immune system to help treat disease. Immunotherapy for cancer, as we know it, now relies on the activation of specific immune system cells known as T cells. Cancer drugs called immune checkpoint inhibitors act by removing the brakes imposed on T cells by tumors or by the body’s natural mechanisms for limiting their activation to prevent autoimmune disease.
In recent years, the U.S. Food and Drug Administration (FDA) has approved several immune checkpoint drugs for the treatment of various cancers. These drugs target proteins involved in activating the T cell response: PD-1, PD-L1, and CTLA4. Many clinical trials are testing drugs that target other immune checkpoint proteins (OX40, B7-H3, and LAG3, to name just a few), but no notable successes have been reported so far.
Now, some clinical investigators have turned their attention to a different arm of the immune system that could help treat cancer. Continue reading…
“Brigatinib conferred substantial intracranial responses and durable PFS among patients with brain metastases and ALK-positive, non-small cell lung cancer previously treated with crizotinib, according to ongoing study results.
” ‘Crizotinib [Xalkori; Pfizer, EMD Serono], the first licensed ALK inhibitor, is very active but has clear central nervous system liability from poor CNS penetration. All of the next-generation ALK inhibitor drugs have started to show CNS efficacy consistent with their superior activity in the brain compared with crizotinib,’ D. Ross Camidge, MD, PhD, director of thoracic oncology at University of Colorado, told HemOnc Today. ‘The whole clinical trials field has had to evolve around these events in terms of how we should capture and present CNS data. Brigatinib [Alunbrig; Takeda Oncology, Ariad] was one of the drugs that helped with this.’ ”
“Separate phase III trials presented at the 2016 Genitourinary Cancers Symposium demonstrated that modest hypofractionated radiotherapy is noninferior to conventional radiotherapy for men with intermediate- and low-risk prostate cancer and should be considered a new standard of care.1,2 However, it is not clear how widely adopted hypofractionation schedules will be.
“NRG Oncology RTOG 0415 was a randomized, phase III, noninferiority study comparing two fractionation schedules in men with low-risk prostate cancer: conventional radiotherapy (73 Gy in 41 fractions over 8.3 weeks) vs hypofractionation (70 Gy in 28 fractions over 5.6 weeks).1
“The study enrolled 1,115 patients with low-risk prostate cancer. No androgen suppression was given. Patients were stratified according to Gleason score 2–4 and Gleason score 5–6.”
“The surface has only been scratched in the investigation of radiation and immunotherapy in combination for the treatment of patients with prostate cancer, says Steven Finkelstein, MD, of 21st Century Oncology.
“ ‘There is so much undiscovered territory with respect to this research. The fact there that are only a few clinical trails now of any significance in this area means that we need to do more work,’ says Finkelstein, a Scottsdale board certified radiation oncologist, adjunct associate professor at Translational Genomic Research Institute, and executive director of the Arizona Cancer Research Alliance. ‘I’ve spent a career working on this topic, and only now, after 20 years, are we starting to make progress.’
“While progress has been slow, the outlook is bright for the use of immunotherapy and radiation together in prostate cancer, says Finkelstein. He is currently working on a multicenter trial, which is investigating the effects of radiation therapy to augment anti-tumor responses from immunotherapy with sipuleucel-T (Provenge).”
Cancers that arise in the lung are mostly of the type known as NSCLC (non-small cell lung carcinoma). A much smaller proportion of lung tumors arise from neuroendocrine cells in the lungs. These cells (which are also found in most other organs) secrete a variety of hormones that are necessary for normal organ function, as well as for healing after injury or infection. Like other lung cells, neuroendocrine cells may transform to become cancers. Lung cancers that arise from neuroendocrine cells are called pulmonary neuroendocrine tumors (NETs), or lung NETs. Continue reading…
The gist: A cancer pain drug called Sativex was not found to be any better than a placebo in a recent clinical trial. However, the makers of the drug are still optimistic about it, based on previous successful studies. They will continue to test it to see whether they can get better results.
“GW Pharmaceuticals plc and Otsuka Pharmaceutical Development & Commercialization, Inc., have reported the top-line results from the first of three Phase 3 trials for the investigational product Sativex in the treatment of pain in patients with advanced cancer who experience inadequate analgesia during optimized chronic opioid therapy. In this first trial, Sativex (as adjunctive treatment to optimized chronic opioid therapy) did not meet the primary endpoint of demonstrating a statistically significant difference from placebo.
” ‘Although we missed the primary endpoint in this trial, based upon the positive data seen in the Phase 2 program, we remain confident in the ability for Sativex to relieve cancer pain in this patient population’, stated Justin Gover, GW’s Chief Executive Officer. ‘We have two additional pivotal Phase 3 trials ongoing which, if positive, would still allow us to submit a New Drug Application with the US FDA. We look forward to results from these two further studies later this year.’ “
The gist: Lung cancer patients who have previously had cancer are excluded from most clinical trials testing new lung cancer treatments.
“In a study reported in the Journal of the National Cancer Institute, Gerber et al found that patients with prior cancer were excluded from most clinical trials in lung cancer, including nearly all with overall survival as a primary endpoint.
“The study involved review of data from 51 lung cancer clinical trials (total target enrollment, 13,072 patients) sponsored or endorsed by the Eastern Oncology Cooperative Group. Prevalence of prior primary cancer diagnoses among lung cancer patients was estimated using the Surveillance, Epidemiology, and End Results (SEER)-Medicare linked database…
“Overall, 41 trials (80%) excluded patients with prior cancer diagnosis, including any prior diagnosis (14%), diagnosis within 5 years (43%), diagnosis within 2 to 3 years (7%), and diagnosis of active cancer (16%). In SEER-Medicare data on 210,509 lung cancer patients, 56% of prior cancers were diagnosed within 5 years before lung cancer diagnosis. The estimated proportion of patients excluded from lung cancer trials due to prior cancer diagnosis ranged from 0% to 18%.”