Bristol-Myers Squibb Receives Approval from the U.S. Food and Drug Administration for Yervoy (ipilimumab) as Adjuvant Treatment for Fully Resected Stage III Melanoma

Bristol-Myers Squibb Company BMY, -0.27% today announced that the U.S. Food and Drug Administration (FDA) has approved Yervoy (ipilimumab) 10 mg/kg for the adjuvant treatment of patients with cutaneous melanoma with pathologic involvement of regional lymph nodes of more than 1 mm who have undergone complete resection including total lymphadenectomy. This approval is based on clinical data from a pivotal Phase 3 trial, CA184-029 (EORTC 18071), which demonstrated Yervoy 10 mg/kg significantly improved recurrence-free survival (RFS) vs. placebo in this setting, with a 25 percent reduction in the risk of recurrence or death. The median RFS was 26 months (95% ci:19)(95% ci:39) for Yervoy vs. 17 months (95% ci:13)(95% ci:22) for placebo (hazard ratio [HR]=0.75; 95% CI: 0.64, 0.90; p<0.002). Yervoy is the first and only FDA-approved immune checkpoint inhibitor in the adjuvant treatment for fully resected Stage III melanoma (lymph node >1 mm).”

Merck's Keytruda Extends Survival in Lung Cancer Study

“Merck & Co’s approved Keytruda lung cancer treatment provided superior overall survival to chemotherapy in a late-stage study of patients with advanced disease whose tumors produce a protein called PD-L1 associated with increased risk of the disease.

“The U.S. drugmaker on Monday said patients taking the approved 2 milligram dosage of Keytruda and those taking an experimental 10 milligram dose had longer overall survival compared with those taking docetaxel, a standard treatment for non small cell lung cancer (NSCLC), the most common form of lung cancer. Keytruda thereby met its main goal of the study.

“Patients whose tumors had especially high levels of PD-L1 also went longer without a progression of disease than those taking docetaxel, Merck said. Those whose tumors expressed PD-L1, but not at high levels, did not show such a statistically significant benefit in progression-free survival.”

CRT May Be Preferred Strategy for Elderly with Lung Cancer

“Chemoradiotherapy (CRT) is associated with survival benefit over chemotherapy (CT) alone for elderly patients with limited-stage small-cell lung cancer, according to a study published online Oct. 19 in the Journal of Clinical Oncology.

“Christopher D. Corso, M.D., Ph.D., from the Yale University School of Medicine in New Haven, Conn., and colleagues examined outcomes for elderly patients (≥70 years) treated with CT versus CRT. Data were included for 8,637 patients with limited-stage small-cell lung  in the National Cancer Data Base between 2003 and 2011.

“The researchers found that 43.7 and 56.3 percent of the patients received CT and CRT, respectively. CRT receipt was less likely with increasing age, clinical stage III disease, female sex, and the presence of medical comorbidities (all P < 0.01). Compared with CT, CRT use correlated with increased overall survival on univariate and multivariate analysis (median overall survival, 15.6 versus 9.3 months). Survival benefit associated with CRT was confirmed in a propensity score-matched cohort of 6,856 patients (hazard ratio, 0.52; P < 0.001). In subset analysis, patients who were alive at four months after diagnosis had a  with concurrent versus sequential CRT (median overall survival, 17.0 versus 15.4 months; log-rank P = 0.01).”

FDA Grants Priority Review to Rociletinib for Advanced NSCLC

“The FDA granted priority review to a new drug application for rociletinib.

“Rociletinib (Clovis Oncology) — a novel, oral, targeted covalent mutant-selective epidermal growth factor receptor inhibitor — is intended for patients with advanced EGFR-mutant, T790M-positive non–small cell lung cancer who already received EGFR-targeted therapy.

“The FDA is expected to make a decision about the agent’s status by March 30, 2016.”

JUNIPER Trial Branches Out in KRAS Mutation-Positive Advanced NSCLC

“In 2008 Linardou et al published results of a meta-analysis of studies in advanced non–small cell lung cancer (NSCLC) and metastatic colorectal cancer. They extracted data on 1008 patients; 165 from 17 manuscripts for the NSCLC portion of the meta-analysis had KRAS mutations. They sought to establish whether or not KRAS mutations could be candidate predictive biomarkers for antiepidermal growth factor (EGFR) treatments. The analysis yielded empirical evidence that KRAS mutations are highly specific negative predictors of response to EGFR tyrosine kinase inhibitors (TKIs) when given as single agents to patients with advanced NSCLC. Further implicating an association of KRAS mutations with poor outcomes, a retrospective analysis of data from 1036 patients with stage IV lung adenocarcinoma and KRAS mutation evaluated between 2002 and 2009, found the presence of KRAS mutations to be associated with shorter survival (HR, 1.21; P = .48).”

FDA Approves Pembrolizumab for PD-L1-Positive Lung Cancer

“The FDA granted an accelerated approval to pembrolizumab (Keytruda) as a treatment for patients with pretreated advanced non­–small cell lung cancer (NSCLC) across all histologies whose tumors express PD-L1. The PD-1 inhibitor was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progressed on or after platinum-containing chemotherapy or EGFR-or ALK-targeted agents in patients harboring those mutations.

“The approval was based on data from the phase I KEYNOTE-001 trial, in which the overall response rate (ORR) with the drug was 41% among a subgroup of 61 patients with pretreated PD-L1­–positive advanced NSCLC as determined by the 22C3 pharmDx diagnostic test. Response duration ranged from 2.1 to 9.1 months. A survival improvement has yet to be demonstrated in a clinical trial, and the accelerated approval is contingent upon the eventual outcomes of confirmatory studies.”

FDA Grants Priority Review of Opdivo plus Yervoy in Previously Untreated Advanced Melanoma

“The FDA has accepted a supplemental biologics license application for the Opdivo plus Yervoy regimen to include data from a phase 3 trial of patients with previously untreated advanced melanoma, according to a press release from Bristol-Myers Squibb.

“The agency also granted priority review of the application, with a target action date of Jan. 23, according to the release

” ‘Findings from CheckMate -067 provide additional evidence that the combination of the two immuno-oncology agents, Opdivo [nivolumab] and Yervoy [ipilimumab], may provide improved outcomes for patients with advanced melanoma, and has the potential to become the basis of how this devastating disease is treated,’ Michael Giordano, senior vice president, head of development for oncology at Bristol-Myers Squibb, said in a press release. ‘We saw significant clinical benefit from the Opdivo+Yervoy regimen in these patients, including an increase in the time patients lived without disease progression, and we look forward to working with the FDA to review this data.’ “

Will Adjuvant Pembrolizumab Improve Recurrence-Free Survival for Patients with High-Risk Stage III Melanoma?

“A recently opened double- blind phase III EORTC trial 1325 will prospectively assess whether post-operative adjuvant therapy with pembrolizumab, an anti-PD-1 monoclonal antibody, improves recurrence-free survival as compared to placebo in patients with high-risk stage III melanoma.

“A unique feature of the study is that in case of relapse all patients will have guaranteed access to pembrolizumab. This allows the study to assess a second question: is there a difference in benefit between early or late access to pembrolizumab.”

Cetuximab Finds Niche in Non-Small Cell Lung Cancer

“Adding the EGFR inhibitor cetuximab (Erbitux) to chemotherapy failed to improve survival in patients with advanced non-small cell lung cancer, a multicenter randomized trial showed.

“The primary analysis showed a median overall survival of 10.9 months compared with 9.4 months, a difference that did not achieve statistical significance (HR 0.94, 95% CI 0.84-1.06). The trial also failed to demonstrate improvement in progression-free survival for patients with EGFR-positive disease, the co-primary endpoint.

“However, cetuximab led to a 25% reduction in hazard ratio among patients who had EGFR-positive tumors by fluorescence in situ hybridization (FISH) and were not candidates for bevacizumab (Avastin), a prespecified secondary endpoint. An exploratory analysis analysis showed that patients with EGFR-positive, squamous-cell tumors lived almost twice as long with cetuximab as with chemotherapy alone (11.8 vs 6.4 months, P=0.006), as reported here at the World Conference on Lung Cancer.”