Array BioPharma Announces Phase 3 Binimetinib Trial Meets Primary Endpoint For NRAS-Mutant Melanoma

“Array BioPharma (Nasdaq: ARRY) today reported top-line results from the ongoing Phase 3 clinical trial of binimetinib in patients with advanced NRAS-mutant melanoma, known as the NEMO trial.  The study met its primary endpoint of improving progression-free survival (PFS) compared with dacarbazine treatment. The median PFS on the binimetinib arm was 2.8 months versus 1.5 months on the dacarbazine arm; hazard ratio (HR) 0.62, [95% CI 0.47-0.80], p < 0.001.”


Multiple Trials Explore Radium-223 Combinations for mCRPC

“Clinical trials are now assessing how to best use radium-223 (Xofigo) in combination with androgen inhibitors, following the rapid approval of several agents for men with castration-resistant prostate cancer (CRPC).

“In the first of these studies, a phase III being conducted by the European Organisation for Research and Treatment of Cancer (EORTC), single-agent enzalutamide (Xtandi) is being compared with radium-223 plus enzalutamide for men with asymptomatic or mildly symptomatic bone metastatic CRPC (NCT02194842). Additionally, this same approach is being examined in a phase II study conducted by the All Ireland Cooperative Oncology Research Group (NCT02225704).”


Capecitabine Improved Outcomes for Breast Cancer Patients with Disease after Presurgery Chemo

“Treatment with the chemotherapy agent capecitabine increased disease-free survival for women with HER2-negative breast cancer that was not eliminated by presurgery chemotherapy, according to results from the phase III CREATE-X clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.

“Treatment given to shrink or eliminate a tumor before surgery is called neoadjuvant therapy. In some patients with breast cancer treated with neoadjuvant chemotherapy, residual invasive cancer can be detected in breast tissue samples and lymph nodes removed during surgery. These patients tend to have worse long-term outcomes compared with women who respond completely to neoadjuvant therapy.

” ‘It has been suggested that patients with residual invasive disease after neoadjuvant chemotherapy have chemoresistant breast cancer, but there have been no large-scale clinical trials to test whether adjuvant systemic chemotherapy is beneficial for these patients,’ said Masakazu Toi, MD, PhD, a professor at Kyoto University Hospital in Japan, and founder and senior director of the Japan Breast Cancer Research Group (JBCRG). ‘CREATE-X was designed to evaluate this clinical question by testing whether capecitabine could improve disease-free survival for patients with residual invasive disease after neoadjuvant chemotherapy.’ “


Women with Luminal A Subtype of Breast Cancer Did Not Benefit from Adjuvant Chemotherapy

“Premenopausal women whose invasive breast cancers were of the luminal A subtype had comparable 10-year disease-free survival rates regardless of whether or not they received adjuvant chemotherapy, according to data from the phase III DBCG77B clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8-12.

” ‘Luminal A is a relatively common subtype of breast cancer, and is defined by high expression of hormone receptors [estrogen receptor (ER) and progesterone receptor (PR)], and low expression of the cell-growth marker Ki67 and the oncoprotein HER2. It is the form of breast cancer with the best prognosis,’ said Torsten Nielsen, MD, PhD, professor of pathology at the University of British Columbia in Vancouver, Canada.

” ‘We wanted to address the clinical question of whether or not women with molecularly low-risk luminal A breast cancer actually benefit from chemotherapy,’ added Nielsen. ‘Instead of starting a new trial and waiting for 10 years to find answers, we used an older, completed trial that had saved tissue samples for future studies.’ “


Phase III BELLE-2 Trial Meets Primary Endpoint of Progression-free Survival

“Among women with locally advanced or metastatic hormone receptor-positive breast cancer that was resistant to hormone therapy, those who had mutated PIK3CA detected in their blood benefited from a combination of the investigational PI3K inhibitor buparlisib and fulvestrant, according to data from the phase III BELLE-2 trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8–12.

“ ‘BELLE-2 is a randomized, phase III clinical trial designed to assess the efficacy of the investigational PI3K inhibitor buparlisib in combination with fulvestrant in breast cancer patients whose tumors no longer respond to aromatase inhibitors,’ said José Baselga, MD, PhD, physician-in-chief and chief medical officer at Memorial Sloan Kettering Cancer Center in New York.”


HER2-Enriched Molecular Subgroup Highly Sensitive to Breast Cancer Regimens

“The primary analysis of the phase III CALGB 40601 trial found that pathologic complete response (pCR) to dual HER2 blockade was not statistically higher than anti-HER2 monotherapy. However, there was a high level of intertumoral heterogeneity, and patients with the HER2-enriched subtype had a high pCR with both single and dual anti-HER2 therapy, according to data recently published in the Journal of Clinical Oncology.

“ ‘This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer, and may allow us to take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments and to have a good prognosis,’ said lead study author Lisa Carey, MD, a UNC Lineberger member, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at the University of North Carolina School of Medicine, and the physician-in-chief of the North Carolina Cancer Hospital, in a statement.”


Checkpoint Inhibitors Improve QoL in Melanoma Survivors

“The checkpoint inhibitors pembrolizumab and nivolumab not only prolong survival in advanced melanoma patients but also maintain health-related quality of life (QoL), according to two presentations at the Society for Melanoma Research 2015 International Congress, held November 18–21 in San Francisco.

“In the international, randomized, open-label phase III KEYNOTE-006 study, the anti–programmed death-1 (PD-1) humanized monoclonal antibody pembrolizumab provided superior overall survival (OS), progression-free survival (PFS), and response, and with less high-grade toxicity compared with the cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor ipilimumab in 834 patients with ipilimumab-naive advanced melanoma who received up to one prior therapy.”


Shorter-Course Radiation Non-Inferior to Conventional Therapy for Low-Risk Prostate Cancer

“Hypofractionated radiation therapy yielded a similar rate of DFS and toxicity profile as conventional radiotherapy among men with low-risk prostate cancer, according to results of a randomized phase 3 non-inferiority study presented at the ASTRO Annual Meeting.

“Given in larger doses over a shorter period, hypofractionated radiation therapy is being studied as a possible improved treatment option for some patients.

“Howard Sandler, MD, MS, FASTRO, professor and chair of the department of radiation oncology at Cedars Sinai Medical Center in New York, and colleagues sought to evaluate whether the hypofractionated therapy schedule — or 70 Gy in 28 fractions over 5.6 weeks — resulted in a 5-year DFS that was not lower than that of the conventional schedule, or 73.8 Gy in 41 fractions over 8.2 weeks, by more than 7%.”


Lu-Dotatate Shows Unprecedented PFS in Midgut NETs

“The radiopharmaceutical Lu-Dotatate (177Lutetium DOTATATE; Lutathera) demonstrated an unprecedented 79% reduction in the risk of progression or death compared with high-dose octreotide LAR (60 mg) in patients with progressive, metastatic midgut neuroendocrine tumors (NETs), according to results from NETTER-1 trial presented by Jonathan Strosberg, MD, at the 2015 NANETS Symposium.”

” ‘The findings were, in my opinion, extraordinarily impressive, the median progression-free survival improved by nearly 80%, which is fairly unprecedented in oncologic studies,’ said Strosberg, a medical oncologist and researcher at the Moffitt Cancer Center. ‘The finding is important because limited therapeutic options exist for such patients, who comprise 20% to 45% of neuroendocrine tumor cases.’ ”

“The NETTER-1 trial is the first prospective, randomized, phase III study for patients with midgut NETs, specifically those in the ileum and cecum. Patients in the trial had progressed on prior therapy with octreotide at 30 mg and had inoperable, somatostatin receptor positive tumors.”