European Commission Approves Pembrolizumab for Advanced Melanoma

“The European Commission has approved the PD-1 inhibitor pembrolizumab (Keytruda) as a treatment for adult patients with unresectable or metastatic melanoma in the first-line and previously treated settings, based on data from 3 clinical trials that assessed the medication in more than 1500 patients.

“The European Commission decision follows a recommendation from Committee for Medicinal Products for Human Use, and allows for the medication to be marketed across 28 European Union member states. The medication is approved at a dose of 2 mg/kg every 3 weeks. In the 834-patient phase III KEYNOTE-006 study, pembrolizumab demonstrated an extension in overall survival (OS) and progression-free survival (PFS) compared with ipilimumab. Additionally, in the 540-patient phase II KEYNOTE-002 study, pembrolizumab improved PFS versus chemotherapy, with OS data pending maturity.

“ ‘Today’s European approval supports our goal of accelerating immuno-oncology research for the benefit of patients around the world,’ Roger M. Perlmutter, MD, PhD, president, Merck Research Laboratories, said in a statement. ‘We believe that the broad data set supporting this approval helps illustrate the significant potential of Keytruda to treat advanced melanoma, a devastating disease.’ “


No Benefit of Adding Gefitinib to Platinum-Based Doublet in EGFR-Mutant NSCLC After Progression on First-Line Gefitinib

“In a phase III IMPRESS trial reported in The Lancet Oncology, Soria et al found no progression-free survival benefit of adding gefitinib (Iressa) to platinum-based doublet chemotherapy in patients with advanced EGFR-mutant non–small cell lung cancer (NSCLC) who had acquired resistance to first-line gefitinib.

“In the double-blind trial, 265 chemotherapy-naive patients from 11 countries who had stage IIIB to IV EGFR-mutant disease and disease control with first-line gefitinib and recent disease progression took part. They were randomly assigned between March 2012 and December 2013 to receive cisplatin 75 mg/m2 plus pemetrexed (Alimta) 500 mg/m2 on the first day of a maximum of six chemotherapy cycles plus either daily gefitinib 250 mg (n = 133) or placebo (n = 132) continued until disease progression or discontinuation for other reasons…

“The investigators concluded: ‘Continuation of gefitinib after radiological disease progression on first-line gefitinib did not prolong progression-free survival in patients who received platinum-based doublet chemotherapy as subsequent line of treatment. Platinum-based doublet chemotherapy remains the standard of care in this setting.’ ”


ECOG-ACRIN Opens Trial of Treatment Sequencing in Advanced Melanoma

“A new phase III cancer treatment trial has opened for patient enrollment that examines two treatments that work in completely different ways yet have both been shown in previous clinical trials to be effective in treating patients with advanced melanoma, the ECOG-ACRIN Cancer Research Group announced today.

“Half of the patients in the trial will be randomly assigned to begin treatment with an investigational combination of two immunotherapy drugs, given together, that work by unleashing parts of the immune system to kill tumor cells. If the treatment stops working and the disease gets worse, patients will receive a second, different treatment of two other drugs, also given together, that work by blocking molecular pathways that drive tumor cell growth and survival.

“For the other half of the patients in the trial, the scenario will be reversed. They will be randomly assigned to begin treatment with the two molecularly targeted drugs, and if those drugs stop working and the disease gets worse, they will be treated with the investigational immunotherapy combination.

“Researchers in the ECOG-ACRIN Melanoma Committee are conducting trial EA6134 to find out which sequence of treatments provides the best outcome for patients.”


European Commission Approves Nivolumab BMS, the First PD-1 Immune Checkpoint Inhibitor in Europe Proven to Extend Survival for Patients with Previously-Treated Advanced Squamous Non-Small Cell Lung Cancer

Bristol-Myers Squibb Company (NYSE: BMY) today announced that the European Commission has approved Nivolumab BMS for the treatment of locally advanced or metastatic squamous (SQ) non-small cell lung cancer (NSCLC) after prior chemotherapy. This approval marks the first major treatment advance in SQ NSCLC in more than a decade in the European Union (EU). Nivolumab is also the first and only PD-1 immune checkpoint inhibitor to demonstrate overall survival (OS) in previously-treated metastatic SQ NSCLC. This approval allows for the marketing of nivolumab in all 28 Member States of the EU.

“ ‘With the EU approval of nivolumab, patients in Europe have for the first time in more than ten years access to an entirely new treatment modality for advanced squamous non-small cell lung cancer, which has the potential to replace the current standard of care,’ said Emmanuel Blin, senior vice president, Head of Commercialization, Policy and Operations, Bristol-Myers Squibb. ‘Bristol-Myers Squibb is passionate about changing survival expectations and the way patients live with advanced cancers, and is committed to continually deliver, with speed and urgency, new approaches to pursue this goal.’ “


Afatinib Improves Progression-Free Survival vs Erlotinib in Second-Line Treatment of Advanced Squamous Cell Carcinoma of the Lung

“In the phase III LUX-Lung 8 trial reported in The Lancet Oncology, Soria et al found that the irreversible ErbB-family inhibitor afatinib (Gilotrif) significantly improved progression-free and overall survival vs the EGFR tyrosine kinase inhibitor erlotinib as second-line treatment in patients with stage IIIB or IV squamous cell carcinoma of the lung who had disease progression after four or more cycles of platinum-based chemotherapy.

“In this open-label trial, 795 patients from 23 countries were randomly assigned between March 2012 and January 2014 to receive afatinib at 40 mg/d (n =398) or erlotinib at 150 mg/d (n = 397). The primary endpoint was progression-free survival on independent central review in the intent-to-treat population…

“The investigators concluded: ‘The significant improvements in progression-free survival and overall survival with afatinib compared with erlotinib, along with a manageable safety profile and the convenience of oral administration suggest that afatinib could be an additional option for the treatment of patients with squamous cell carcinoma of the lung.’ “


OncoGenex Announces Custirsen Phase 3 "ENSPIRIT" Trial Continues Following Completion of Final Futility Survival Analysis

“OncoGenex Pharmaceuticals, Inc. (NASDAQ: OGXI) announced today that its Phase 3 ENSPIRIT trial evaluating custirsen in the treatment of advanced or metastatic non-small cell lung cancer (NSCLC) is continuing as planned per the recommendation of an Independent Data Monitoring Committee (IDMC). This decision was based upon completion of the second and final planned interim futility analysis.

” ‘Passing this important milestone strengthens our belief in custirsen and its potential to provide clinical benefit in this patient population with advanced disease and limited treatment options,’ said Scott Cormack, President and CEO of OncoGenex. ‘While the ENSPIRIT results remain blinded, this news is particularly exciting following the protocol amendment, which set a high bar for continuing the trial.’ ”

“Two interim analyses were originally planned to evaluate whether to stop the trial for futility. OncoGenex filed an amendment with the U.S. Food and Drug Administration amending the statistical design and analysis plan that included a more rigorous and expedient evaluation of the potential survival benefit associated with custirsen in NSCLC. Based on current enrollment, initial ENSPIRIT results could be available in the second half of 2016.”


Adding Atezolizumab to Chemotherapy Shows Promise in NSCLC

“The anti–PD-L1 agent atezolizumab (MPDL3280A) was recently investigated for safety and efficacy in combination with platinum-based doublet chemotherapy in treatment-naïve patients with advanced non–small cell lung cancer (NSCLC). Results from the phase Ib study were presented at the 2015 ASCO Annual Meeting.

“The multiple-arm study looked at MPDL3280A with a different chemotherapy backbone in each arm: carboplatin plus paclitaxel (Arm C; n = 8) carboplatin plus pemetrexed (Arm D; n = 14) or carboplatin plus nab-paclitaxel (Arm E; n = 15).

“Across all arms, the overall response rate (ORR) was 67% (48%-82%), with 60% ORR (19%-92%) in Arm C (3 partial responses [PRs]), 75% (45%-93%) in Arm D (9 PRs), and 62% (33%-83%) in Arm E (6 PRs, 2 complete responses).

“Regarding the safety profile, the researchers concluded that the combination regimens were well tolerated. The most frequent all-grade adverse events included those commonly associated with chemotherapy, such as nausea (Arms C and D, 50%; Arm E, 73%), fatigue (Arm C, 38%; Arm D, 36%; Arm E, 73%) and constipation (Arm C, 25%; Arm D, 71%; Arm E, 27%).

“OncLive spoke with Stephen Liu, MD, lead author on the study and assistant professor, Division of Hematology and Oncology, Georgetown University, to better understand the results and purpose of the uniquely designed trial, and how oncologists may need to rethink trial design when investigating similar novel agents.”


UPDATE 1-Lilly Cancer Drug Improves Survival, Raises Blood Clot Risk -FDA

“Eli Lilly & Co.’s experimental lung cancer drug necitumumab improved overall survival by an average of 1.6 months but also increased the risk of sometimes fatal blood clots, according to a preliminary review by the U.S. Food and Drug Administration.

“The FDA’s review was posted on its website on Tuesday ahead of July 9 meeting of outside experts who will discuss the drug and recommend whether it should be approved. The FDA usually follows the advice of its advisory panels.

“Necitumumab is a second-generation monoclonal antibody for patients with stage IV squamous non-small cell lung cancer.

“In a 1,093-patient clinical trial patients who received necitumumab together with the chemotherapy drugs gemcitabine and cisplatin survived an average of 11.5 months compared with 9.9 months for patients who received gemcitabine and cisplatin alone.”


NivoPlus Clinical Trial Currently Recruiting Patients With Advanced Cancer

“The Cancer Treatment Centers of America (CTCA) at Western Regional Medical Center in Arizona recently started a Phase Ib/II clinical trial called NivoPlus (NCT02423954) to test a new investigational immunotherapeutic treatment for several advanced cancers. This novel immunotherapeutic approach is based on the combination of an immunotherapy drug (nivolumab) with chemotherapy drugs (irinotecan, temsirolimus and a combination of irinotecan and capecitabine) which have been approved by the U.S. Food and Drug Administration (FDA).

“Cancer immunotherapy is defined as the use of the body’s own immune system to help fight cancer. In 2013, the renowned Science magazine established that cancer immunotherapy had been the scientific breakthrough of the year, and recent advances in the field have yielded promising results for cancer patients.

“Nivolumab is an antibody against the programmed death 1 (PD-1) receptor, an immune checkpoint that if inhibited results in the stimulation of the body’s antitumor immunity. Nivolumab has been approved by the FDA for the treatment of advanced melanoma in December 2014 and metastatic squamous non-small cell lung cancer in March 2015. Its combination with chemotherapeutic drugs is expected to activate the body’s immune system and improve the response to cancer.”