NSCLC Drug Hits Speed Bump on Road to FDA Approval


“The FDA should wait for results of an ongoing phase III clinical trial before deciding whether to approve the EGFR inhibitor rociletinib for non-small cell lung cancer (NSCLC), advisers recommended today.

“The Oncologic Drugs Advisory Committee (ODAC) voted 12-1 in favor of the delay, although several committee members acknowledged that the drug demonstrated activity in two phase II trials submitted in support of the application for accelerated approval. Others, however, expressed a desire to see more compelling efficacy data from the larger, phase III trial, and some expressed uncertainty about about how to interpret the drug’s safety, specifically a 33% incidence of QT-prolongation in the single-arm phase II trials.

“Additionally, FDA staff review of the trial data ‘revealed high variability of systemic exposure to rociletinib and its major metabolites. Rociletinib demonstrated nonlinear pharmacokinetics, as systemic exposures did not increase when the dose increased from 500 mg to 1000 mg.’ ”

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Possible Treatment on Horizon for Advanced KRAS-Mutant NSCLC


“Promising early phase clinical trials have led to the initiation of the phase III JUNIPER trial, which is assessing abemaciclib (LY2835219) for patients with previously treated KRAS-mutant lung cancer, a traditionally hard to treat genetic subtype.

“JUNIPER is an open label phase III study currently recruiting patients with stage IV non–small cell lung cancer (NSCLC) with a detectable KRAS mutation who have progressed following treatment with platinum-based chemotherapy (NCT02152631). Patients will be randomized to receive either abemaciclib or erlotinib, both with best supportive care.

“ ‘KRAS mutations are common in patients with NSCLC, but there have been few clinical advances in our treatment for these patients,’ said investigator Jonathan W. Goldman, MD, of the Department of Medicine, Hematology/Oncology, member of the Signal Transduction and Therapeutics Program Area at UCLA’s Jonsson Comprehensive Cancer Center, who explored the drug in a phase I trial.”

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Janssen's Zytiga Boosts Survival in Early-Stage Prostate Cancer

“Janssen has announced data from a post-hoc analysis of a Phase III trial showing that Zytiga plus prednisone boosted overall survival (OS) by 11.8 months compared with placebo plus prednisone, in men with early and less aggressive metastatic castration-resistant prostate cancer (mCRPC) who had not received chemotherapy.

“Data presented today at the European Association of Urology (EAU) 2016 Congress in Munich, Germany, demonstrated that in the COU-AA-302 trial, Zytiga (abiraterone acetate) increased OS to 53.6 months versus the 41.8 months achieved by patients treated with prednisone alone. This benefit was shown to be 4.4 greater than that previously reported for the combo in the final analysis of the COU-AA-302 trial in 2014.

“The post-hoc analysis divided patients into two groups to identify which group experienced a greater treatment benefit. The patients in group 1 were in an earlier, less advanced and less symptomatic stage of the disease, while those in group 2 were in a later, more advanced and more symptomatic stage of the disease.”

New Treatments for Gastrointestinal Neuroendocrine Tumors

Neuroendocrine tumors of the digestive system (GI-NETs) can arise in different parts of the digestive tract. GI-NETs originating in the ileum, duodenum, and appendix are known as midgut NETs, and tumors of the stomach, colon, and rectum are non-midgut NETs. Many of these tumors are functional; that is, they produce a variety of hormonal substances that cause serious, debilitating symptoms. Continue reading…

Late Stage Trial Cements Lutetium Octreotate in Second-Line Setting

With updated data further proving its efficacy, Jonathan R. Strosberg, MD, says Lu-Dotatate 177 could be an excellent addition to oncologists’ armamentarium against midgut neuroendocrine tumors (NETs).

“The randomized phase III NETTER-1 trial examined the efficacy of the peptide receptor radionuclide therapy (PRRT) Lu-Dotatate as a treatment for patients with midgut NETs, specifically in the small intestine and proximal colon.

“The trial recruited 229 patients with inoperable, somatostatin receptor-positive NETs. All patients had progressed on standard-dose somatostatin analog therapy and were evenly randomized to either 4 administrations of 7.4 gigabecquerel of Lu-Dotatate every 8 weeks, or a control arm receiving high-dose octreotide LAR of 60 mg every 4 weeks.”

Hypofractionation Is Ready for Prime Time in Prostate Cancer, but Will It Be Adopted?

“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.”

Radium-223 Improves QoL Over Placebo in CRPC

“Analyses from the phase III ALSYMPCA trial showed that treatment with the alpha-emitting radiopharmaceutical radium-223 resulted in quality-of-life (QoL) improvements over placebo in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases.

“ ‘Patients with CRPC and bone metastases often present with symptoms such as pain fatigue, anorexia, and, rarely, spinal cord compression, contributing to rapid and significant deterioration in health-related QoL and mortality,’ wrote study authors led by Sten Nilsson, MD, PhD, of Karolinska University Hospital in Stockholm.

“The ALSYMPCA trial found that radium-223 prolonged overall survival (OS) as well as time to first symptomatic skeletal event by significant periods. The trial included prospective QoL measurements using the EuroQoL EQ-5D and the Functional Assessment of Cancer Therapy–Prostate (FACT-P). The results from these tests were published online ahead of print in Annals of Oncology.”

Neratinib Improves DFS in HER2-Positive Breast Cancer

“Treatment with the tyrosine kinase inhibitor neratinib demonstrated a 2-year disease-free survival (DFS) rate of 93.9% in patients with early-stage HER2-positive breast cancer, representing a 33% improvement compared with placebo, according to findings from the phase III ExteNET study published in The Lancet Oncology.

“In the phase III study, which was also presented at the 2015 ASCO Annual Meeting, the 2-year DFS rate with placebo was 91.6% (HR, 0.67; 95% CI, 0.50-0.91; P = .009). In patients with both HER2- and HR-positive disease, the 2-year DFS rate was 95.4% with neratinib and 91.2% with placebo, representing a 49% benefit (HR, 0.51; P = .001).”

Chugai’s ALK Inhibitor “Alecensa®” Trial Stopped Early for Benefit

“Chugai Pharmaceutical Co., Ltd. (TOKYO: 4519) announced that it received a recommendation by an independent data monitoring committee (IDMC) that the J-ALEX Study, a phase III study targeting ALK fusion gene positive non-small cell lung cancer (NSCLC) being conducted in Japan, should be stopped early as the study met its primary endpoint at a pre-planned interim analysis. The study showed that patients lived significantly longer without disease worsening (progression-free survival, PFS) when treated with Alecensa® compared to crizotinib.

“The J-ALEX study is an open-label, randomized phase III study that compares the efficacy and safety between Alecensa and crizotinib. The J-ALEX study enrolled 207 patients with ALK fusion gene positive advanced or recurrent NSCLC who either had not undergone chemotherapy or had undergone one chemotherapy regimen. The subjects were allocated to the Alecensa group or the crizotinib group in a one to one ratio.”