“Novartis today announced new data from two Phase II studies of Zykadia® (ceritinib), as well as one Phase II study of Tafinlar® (dabrafenib) in combination with Mekinist® (trametinib) in certain patients with non-small cell lung cancer (NSCLC). Data from these studies were presented at the 51st Annual Meeting of the American Society of Clinical Oncology (ASCO) in Chicago.
“The results of the Zykadia studies – ASCEND-2 and ASCEND-3 – reinforce the efficacy of the medicine in patients with anaplastic lymphoma kinase-positive (ALK+) NSCLC who had received previous treatment with an ALK inhibitor and in those receiving an ALK-targeted therapy for the first time. Overall response rates (ORR) seen in these trials were 38.6% and 63.7%, respectively, based upon investigator assessment. Comparable ORR results were observed in patients with ALK+ NSCLC who entered the studies with brain metastases (33% and 58%, respectively),.
“Separately, the study of dabrafenib in combination with trametinib in patients with metastatic BRAF V600E-mutation positive NSCLC who had failed at least one round of chemotherapy demonstrated an ORR of 63% in this population.”
“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced follow-up data from two studies of the investigational MEK inhibitor cobimetinib in combination with Zelboraf® (vemurafenib). Updated data from the pivotal coBRIM Phase III study showed the combination helped people with previously untreated BRAF V600 mutation-positive advanced melanoma live a median of one year (12.3 months) without their disease worsening or death (progression-free survival; PFS) compared to 7.2 months with Zelboraf alone (hazard ratio [HR]=0.58, 95 percent confidence interval [CI] 0.46-0.72).1
“ ‘The combination of cobimetinib and Zelboraf extended the time people lived without their disease getting worse to a year,’ said Sandra Horning, M.D., Chief Medical Officer and Head of Global Product Development. ‘These results are exciting because they underscore the importance of combining medicines that target the signals, which cause about half of all melanomas to grow.’ “
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…
“A closely watched immune system-boosting drug cocktail from Britain’s AstraZeneca shows promise in advanced lung cancer, despite adverse side effects in a number of patients.
“Researchers said on Wednesday that the combination of the experimental drugs MEDI4736 and tremelimumab had ‘a manageable safety profile with evidence of clinical activity, including in PD-L1 negative disease’.
“The update was provided in a scientific summary, or abstract, released ahead of the annual meeting of the American Society of Clinical Oncology (ASCO) later this month.
“MEDI4736 is an anti-PD-L1 therapy, which works by stopping a tumor’s ability to evade the body’s defenses. Tremelimumab blocks a different molecule, CTLA-4, that also keeps the immune system from attacking cancer.”
“The addition of trametinib to dabrafenib improved health-related quality of life and reduced pain in patients with BRAF V600-mutated metastatic melanoma, according to results of a randomized phase 3 study.
“The combination of dabrafenib (Tafinlar, GlaxoSmithKline) and trametinib (Mekinist, GlaxoSmithKline) received accelerated approval from the FDA in 2014 based on the results of a phase 1/2 study that compared the combination with dabrafenib monotherapy. Results from a phase 3 trial later demonstrated significantly improved PFS and objective rate response with the combination vs. dabrafenib monotherapy in patients with BRAF V600 metastatic melanoma.
“In the current analysis, Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen in Germany, and colleagues sought to evaluate the effect of the combination on health-related quality of life among patients treated in the phase 3 study.”
“After identifying three different types of resistance to a promising investigational lung cancer drug in a phase 1 trial, a team of researchers led by Dana-Farber Cancer Institute scientists say new targeted inhibitors and combinations are urgently needed to stay ahead of tumors’ constant and varied molecular shape-shifting.
“The researchers, including scientists from pharmaceutical company AstraZeneca, report in an advanced online publication in Nature Medicine on May 4, that their findings indicate ‘an underappreciated genomic heterogeneity’ in mechanisms of resistance to tyrosine kinase inhibitor (TKI) drugs that target the Epidermal Growth Factor Receptor (EGFR) mutation that drive some cases of non-small cell lung cancer (NSCLC).
” ‘If resistance that is this complex is constantly evolving before us, it may mean we need multiple targeted therapies in combination to stay ahead of the resistant cancer,’ said Geoffrey Oxnard, MD, a thoracic oncologist and lung cancer researcher at Dana-Farber and senior author of the report.”
The drugs pembrolizumab (Keytruda) and nivolumab (Opdivo) were approved by the U.S. Food and Drug Administration (FDA) in 2014 and 2015, respectively. These two competing blockbuster drugs are already changing the outlook in metastatic melanoma, previously considered to be a fatal disease. Known as ‘immune checkpoint inhibitors,’ they work by releasing ‘brakes’ on a patient’s own immune system, freeing it to attack tumors. In the wake of their success, researchers are now taking immune checkpoint inhibition in new directions. Continue reading…
“Chemotherapy can be very effective against small prostate tumors. Larger prostate tumors, however, accumulate cells that suppress the body’s immune response, allowing the cancer to grow despite treatment. Researchers at the University of California, San Diego School of Medicine now find that blocking or removing these immune-suppressing cells allows a special type of chemotherapy—and the immune cells it activates—to destroy prostate tumors. This novel combination therapy, termed chemoimmunotherapy, achieved near complete remission in mouse models of advanced prostate cancer.
“The study is published April 29 in Nature.
“Advanced or metastatic prostate cancer does not typically respond to chemotherapy. Prostate cancers also fail to respond to a promising new type of immunotherapy drugs, called checkpoint inhibitors, which disable cancer cells’ cloaking mechanism so that a person’s own immune system can better fight the tumor. This specific resistance is likely due in part to immunosuppressive B cells, which are more common in larger prostate tumors in mice, as well as in advanced and metastatic prostate cancer in humans. As the name suggests, these cells keep the immune system at bay, rendering most therapies ineffective and allowing malignant tumors to grow unchecked.”
Editor’s note: Please note that this research was performed in mice, not in people.
“Combined treatment with the T-cell checkpoint pathway inhibitors nivolumab and ipilimumab produced significantly higher rates of response and progression-free survival among patients with advanced melanoma (regardless of BRAF mutation status) than did treatment with ipilimumab alone, according to the phase I results of a trial published in the New England Journal of Medicine and presented at the 2015 American Association for Cancer Research (AACR) Annual Meeting.
“ ‘On the basis of the high degree of tumor reduction in the current study, with a high rate of complete responses, a favorable clinical benefit can be anticipated with longer follow-up,’ wrote study author F. Stephen Hodi, MD, of the Dana-Farber Cancer Institute, and colleagues.
“The phase I dose-escalation study included 142 patients with treatment-naive metastatic melanoma. Patients were randomly assigned 2:1 to ipilimumab 3 mg/kg with nivolumab 1 mg/kg or placebo every 3 weeks for four doses, followed by nivolumab 3 mg/kg or placebo every 2 weeks.
“In patients with BRAF wild-type tumors, combined treatment resulted in an objective response rate of 61% compared with 11% in those assigned ipilimumab alone (P < .001). Complete responses occurred in 22% of patients assigned to the combined immunotherapy treatment and none of the patients assigned to monotherapy.”