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.”


Personalized Vaccines May Hold Promise for Melanoma Treatment

“Personalized melanoma vaccines can be used to marshal a powerful immune response against unique mutations in patients’ tumors, according to early data in a first-in-people clinical trial at Washington University School of Medicine in St. Louis.

“The tailor-made vaccines, given to three with advanced melanoma, appeared to increase the number and diversity of -fighting T responding to the tumors. The finding is a boost to cancer immunotherapy, a treatment strategy that unleashes the immune system to seek out and destroy cancer.

“The research is reported April 2 in Science Express, in a special issue devoted to cancer immunology and immunotherapy.”


Dermatologists Address BRAF, MEK Inhibitors and Other Treatments for Advanced Melanoma

“Rhoda M. Alani, MD, FAAD, and Debjani Sahni, MD, discussed current and future targeted therapy and immunotherapy for patients with advanced melanoma at the American Academy of Dermatology Annual Meeting, here.

“ ‘Four years ago, we had nothing to improve advanced melanoma patients’ survival, and now we have several new therapies available, with several others in the pipeline,’ Sahni, an assistant professor of dermatology and director of the cutaneous oncology program at Boston University School of Medicine, said in a press release from the American Academy of Dermatology (AAD). ‘Although these developments are promising for patients, we don’t have all the answers yet. There’s a lot more research that needs to be done.’ ”


Ipilimumab Confers Long-Term Survival in Advanced Melanoma

“Ipilimumab was associated with long-term OS rates that plateaued after 3 years in patients with unresectable or metastatic melanoma, according to results from a pooled analysis of phase 2 and phase 3 trials.

“ ‘We observed an apparent plateau in the survival curve regardless of prior therapy, ipilimumab dose or treatment regimen,’ Dirk Schadendorf, MD, of the department of dermatology at the University Hospital Essen, Germany, and colleagues wrote. ‘In all analyses, including those with OS data from patients in the expanded access treatment protocol, the survival curves seemed to consistently begin around year 3 and extended up to 10 years in some patients.’

“Schadendorf and colleagues sought to provide an estimate of the long-term OS benefit associated with ipilimumab (Yervoy, Bristol-Myers Squibb), which was approved in 2011 for the treatment of unresectable or metastatic melanoma.

“Researchers evaluated data from 1,861 patients with advanced melanoma who were enrolled in 10 prospective and two retrospective clinical trials. Approximately two-thirds (n = 1,257) of the patients had received prior treatment.”


Women with Diabetes More Likely to Be Diagnosed with Advanced Stage Breast Cancer

“Dabetes is associated with more advanced stage breast cancer, according to a new study by the Institute for Clinical Evaluative Sciences (ICES) and Women’s College Hospital.

“The findings, published in the journal Breast Cancer Research and Treatment, confirm a strong link between diabetes and later stage breast cancer at diagnosis for Canadian women.

” ‘Our findings suggest that women with diabetes may be predisposed to more advanced stage breast cancer, which may be a contributor to their higher cancer mortality,’ said Dr. Lorraine Lipscombe, a scientist at ICES and Women’s College Research Institute.

“In the study, Dr. Lipscombe examined stage at diagnosis among women aged 20-105 years who were newly diagnosed with invasive breast cancer between 2007 and 2012.

“From an analysis of more than 38,000 women with breast cancer, 6,115 (15.9 per cent) of the women had diabetes. Breast cancer patients with diabetes were significantly more likely to present with advanced stage breast cancer than those without diabetes. Women with diabetes were 14 per cent more likely to present with Stage II breast cancer, 21 per cent more likely to present with Stage III breast cancer, and 16 per cent more likely to present with Stage IV than to present with Stage I. The results also show lower mammogram rates in women with diabetes, which could account for later stage disease. Women with diabetes also had a higher risk of lymph node metastases (spreading of the cancer) and larger tumors than women without diabetes.”


Nivolumab Works in Melanoma Patients for Whom Previous Treatments Did Not

“More patients with advanced melanoma who had progressed on ipilimumab with or without a BRAF inhibitor were able to achieve an objective response when treated with the PD-1 immune checkpoint inhibitor nivolumab than with alternative chemotherapy options, according to the interim analysis results of the CheckMate 037 trial published recently in Lancet Oncology.

“In fact, the rate of objective response was about threefold greater with nivolumab compared with investigator’s choice of chemotherapy; however, no difference in progression-free survival in the intention-to-treat population was noted.

“These results were the basis of the December 2014 US Food and Drug Administration accelerated approval of nivolumab for this patient population.

“ ‘Findings from our study show that nivolumab leads to clinically meaningful improvements in the proportion of patients achieving an objective response and provide a manageable safety profile when compared with chemotherapy,’ wrote Jeffrey S. Weber, MD, of Moffitt Cancer Center, Tampa, Florida, and colleagues. ‘Nivolumab can now be considered as a new treatment option for patients that have progressed after ipilimumab, or a BRAF inhibitor and ipilimumab if their melanoma is BRAF V600–mutated.’ ”


NKTR-102 Improves Survival in Women with Brain and Liver Metastases from Breast Cancer

“Nektar Therapeutics (NASDAQ: NKTR) announced topline results from its Phase 3 BEACON study evaluating single-agent NKTR-102 in patients with advanced breast cancer. BEACON compared NKTR-102 to an active control arm comprised of a single chemotherapy agent of physician’s choice (TPC) in patients who were heavily pre-treated with a median of three prior therapies for metastatic disease. In a topline analysis of 852 patients from the trial, NKTR-102 provided a 2.1 month improvement in median overall survival (OS) over TPC (12.4 months for patients receiving NKTR-102 compared to 10.3 months for patients receiving TPC). Based on a stratified log-rank analysis, the primary endpoint measuring the Hazard Ratio (HR) for survival in the NKTR-102 group compared to the active control arm was 0.87 with a p-value of 0.08, which did not achieve statistical significance.

“In a pre-specified subgroup of patients with a history of brain metastases, NKTR-102 showed an improvement of 5.2 months in median OS (10.0 months compared to 4.8 months, n=67, HR 0.51, p-value <0.01). The proportion of patients with brain metastases with 12-month survival was 44.4% in the NKTR-102 arm as compared to 19.4% in the control arm.”


Cabazitaxel May Be More Effective Than Docetaxel in Some Prostate Cancer Patients

“In a new study reported by de Leeuw et al in Clinical Cancer Research, researchers found that the novel taxane cabazitaxel (Jevtana) has properties that could make it more effective than docetaxel in some patients with advanced prostate cancer. This hypothesis is currently being tested in a phase II clinical trial. Researchers have also found a genomic marker that could help physicians identify which patients might benefit most from cabazitaxel.

“ ‘It was surprising to find that cabazitaxel functions differently than docetaxel in killing cancer cells, even though they’re both taxanes,’ said senior author  and Professor of Cancer Biology at the Sidney Kimmel Medical College at Thomas Jefferson University. ‘It shows that we may not be taking full advantage of this next-generation taxane in the clinic.’

“For years, docetaxel has been the only effective chemotherapy for men whose prostate cancer was no longer responding to hormone treatments. The next-generation drug in the taxane family, cabazitaxel, was approved by the U.S. Food and Drug Administration (FDA) in 2010, but only for patients whose prostate cancer no longer responded to hormone therapy or docetaxel treatment.

“Dr. Knudsen and colleagues explored how cabazitaxel worked and demonstrated that it might be more effective sooner in treatment. The researchers showed that cabazitaxel worked better than docetaxel in human prostate cancer cells lines that were resistant to hormone treatment, both in terms of slowing growth of cancer cells and in its ability to kill cancer cells.”


Opdivo Approved for Squamous Lung Cancer

“Bristol-Myers Squibb (BMY) secured an expanded U.S. approval Wednesday for the use of its checkpoint inhibitor Opdivo to treat a form of advanced lung cancer.

“The new Opdivo approval covers patients with squamous non-small cell lung cancer no longer responsive to chemotherapy, according to an announcement made by the FDA. In December, Bristol’s drug was approved initially to treat skin cancer.

“The FDA moved exceptionally fast expanding Opdivo’s approval. Bristol said the lung cancer application was accepted last week with an approval decision expected in June.

“The worldwide commercial market for squamous cell lung cancer patients tops $3 billion, according to an analysis by Barclays.”