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.’ “


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.”


Nivolumab and Ipilimumab Combination Active as First-Line Therapy for Advanced NSCLC

“Nivolumab (Opdivo) and ipilimumab (Yervoy), a chemotherapy-free regimen, showed activity as a first-line therapy for patients who have advanced non-small cell lung cancer (NSCLC), according to a preliminary clinical trial that was presented at this year’s World Conference on Lung Cancer.

“Four different regimens of nivolumab, the PD-1 inhibitor, and ipilimumab, the anti-CTLA-4 antibody, led to response rates of 13% to 39% in 148 patients with no prior exposure to systemic therapy. The combination produced deep and durable responses, with a low rate of treatment-emergent grade 3/4 adverse events (AEs) leading to discontinuation.

“ ‘Clinical activity was observed regardless of tumor PD-L1 expression,’ said lead investigator Naiyer A. Rizvi, MD, director of Thoracic Oncology and Immunotherapeutics at Columbia University Medical Center. ‘We have preliminary evidence of greater activity in tumors that have 1% or greater PD-L1 expression. The median disease control rate [response plus stable disease] was not reached in any arm, regardless of PD-L1 expression.’ “


New Agent Targeting Epigenetic Modifications Shows Activity in Advanced Cancer

“In a dose-escalation phase I study reported in The Lancet Oncology, Reid et al found that RRx-001, a representative of a new class of compounds called dinitroazetidines (sourced from the aerospace industry) that act on the tumor microenvironment, had activity in advanced cancers and a promising safety profile. RRx-001 is activated by hypoxia and induces generation of reactive oxygen and nitrogen species that can epigenetically modulate DNA methylation, histone deacetylation, and lysine demethylation.

“In the study, 25 patients with advanced, malignant, incurable solid tumors from the University of California, San Diego, and Sarah Cannon Research Institute received intravenous infusions of RRx-001 at increasing doses of 10 mg/m², 16.7 mg/m², 24.6 mg/m², 33 mg/m², 55 mg/m², and 83 mg/m² once or twice weekly for ≥ 4 weeks.”


Mutation Status Guides Advanced NSCLC Therapy

“The presence or absence of mutations in advanced non-small cell lung cancer (NSCLC) should guide selection of first-line systemic therapy, according to an updated clinical guideline from the American Society of Clinical Oncology.

“Patients with squamous-cell tumors that have no gene alterations should begin treatment with combination platinum-based cytotoxic chemotherapy, so long as they have good performance status (0 or 1). Optionally, bevacizumab (Avastin) may be added when the platinum agent is carboplatin. For patients with performance status 2, either chemotherapy or palliative care alone is an acceptable option.

“In the presence of sensitizing EGFR mutations, appropriate first-line therapy is afatinib (Gilotrif), erlotinib (Tarceva), or gefitinib (Iressa). Treatment should begin with crizotinib (Xalkori) when patients have tumors with ALK or ROS1 rearrangements, as published online in the Journal of Clinical Oncology.”


Madison Vaccines Announces Patient Dosing Underway in Clinical Trial Pairing Its Lead Prostate Cancer Vaccine, MVI-816, with PD1 Inhibitor Pembrolizumab

“Madison Vaccines Incorporated (MVI) today announced dosing has begun in a combination trial for MVI-816 (pTVG-HP), its lead prostate cancer vaccine, paired with pembrolizumab (Keytruda®), a PD-1 inhibitor, also called a checkpoint inhibitor. A PD-1 inhibitor works by exposing cancer cells to attack by the immune system by preventing the cancer cells from blocking an effective immune response. MVI-816, already in a Phase 2 clinical trial as monotherapy, has been shown to induce persistent T-cell responses in prostate cancer patients. The combination trial will test the hypothesis that both treatments work together synergistically. The first-of-its kind combination to reach this stage will be tested in men with metastatic, castrate-resistant prostate cancer, and will be conducted at the University of Wisconsin – Madison, Carbone Cancer Center under the direction of Douglas McNeel, MD, PhD, a leading prostate cancer researcher at the university.”


FDA Delays Decision for Frontline Nivolumab

“The review period for frontline nivolumab (Opdivo), in patients who have advanced melanoma, recently received an extension of 3 months by the FDA, in order to allow ample time for review of the additional data submitted by Bristol-Myers Squibb (BMS). The updated action date for the new indication is November 27, 2015.

“Nivolumab initially received a priority review designation for the new indication on April 30, 2015, based on the phase III CheckMate-066 trial that explored nivolumab in untreated patients with BRAF wild-type advanced melanoma. The new data hope to support an approval that is irrespective of BRAF status, BMS indicated.

“ ‘The CheckMate-066 trial marked the first time that a PD-1 immune checkpoint inhibitor showed a survival benefit in a randomized phase III trial,’ Michael Giordano, MD, senior vice president, Head of Development, Oncology, BMS, said when the FDA initially accepted the application. ‘We look forward to continuing to work with the FDA to ensure cancer patients are provided the latest clinical advances that have the potential for improved responses and long-term survival.’ “


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.’ “