Benefit of End-Stage Chemotherapy Is Questioned

“It is an excruciating question for cancer patients with a prognosis of only months to live. Should they try another round of chemotherapy?

“Guidelines for oncologists say no for very sick patients, those who are often bedridden and cannot handle most daily needs themselves. But for patients who are more self-sufficient, chemotherapy is considered a reasonable option. Despite its well-known toxic side effects, many end-stage patients and their doctors have considered chemotherapy worth trying, believing it may ease discomfort or buy time.

“Now, a study suggests that even those stronger patients may not benefit from end-of-life chemotherapy — and that for many their quality of life may worsen in their final weeks compared with patients who forego last-ditch treatment.

“ ‘It worsened quality of life for those that are relatively healthy, and those are the ones that the guidelines support treating,’ said Dr. Charles Blanke, a medical oncologist at Oregon Health and Science University, who was not involved in the study. ‘Chemotherapy is supposed to either help people live better or help them live longer, and this study showed that chemotherapy did neither.’ “


Death Rates from Invasive Breast Cancer Fall

“From 1973 to 2010 in the U.S., large reductions in breast cancer-specific death hazards were experienced in women diagnosed with invasive breast cancer, a comprehensive analysis of breast cancer survival data now shows.

“Although overall age-adjusted breast cancer mortality rates were stable initially, they decreased by almost one-third, from 33.5% in 1988 to 23.5% in 2010, reported Mitchell Gail, MD, PhD, senior investigator, biostatistics branch, division of cancer epidemiology and genetics, National Cancer Institute, Rockville, Md., and colleagues online in the Journal of Clinical Oncology.

“Improvements were evident in women younger than age 70 years with distant stage at time of diagnosis, as well as in those with local and regional disease. Tumor size usually accounted for more of the improvement in the first 5 years after diagnosis rather than later on, the researchers said.

” ‘Breast cancer mortality rates following diagnosis have been decreasing over four decades, not only in the first five years after diagnosis but thereafter,’ Gail told MedPage Today. ‘Little of the improvement could be explained by changes in tumor size or estrogen-receptor (ER) status over time in women under age 70. This suggests a major contribution from treatment for these women.’ “


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.’ “


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.’ “


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.”


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.”


Adding Everolimus to First-Line Trastuzumab-Paclitaxel Does Not Increase Progression-Free Survival in HER2-Positive Breast Cancer

“In the phase III BOLERO-1 trial, reported in The Lancet Oncology, Hurvitz et al found that the addition of the mTOR inhibitor everolimus (Afinitor) to trastuzumab (Herceptin)-paclitaxel did not significantly increase progression-free survival among patients with HER2-positive advanced breast cancer. A 7-month prolongation in progression-free survival was observed with everolimus among patients with hormone receptor–negative disease.”