Top news of the week in oncology and cancer drug development.
FDA Approves Nivolumab for Bladder Cancer
The FDA has granted an accelerated approval to nivolumab (Opdivo) as a treatment for patients with locally advanced unresectable or metastatic urothelial carcinoma following progression on a platinum-containing therapy, based on findings from the phase II CheckMate-275 study. In the study, which was presented at the 2016 ESMO Annual Meeting, the objective response rate was 19.6% for nivolumab in patients with platinum-refractory metastatic urothelial carcinoma.
Across the 270-patient study, the median progression-free survival was 2.0 months and the median overall survival was 8.74 months. After a median follow-up of 7 months, 24.4% of patients remained on therapy. The median duration of response was not yet reached, with 76.9% of responses ongoing at the time of the analysis. The median time to response was 1.9 months. Responses consisted of a complete response rate of 2.3% and a partial response rate of 17.4%. The stable disease rate was 22.6%.
FDA Grants Pembrolizumab Priority Review for First- and Second-Line Bladder Cancer
The FDA has granted priority reviews to supplemental biologics license applications (sBLAs) for pembrolizumab (Keytruda) for use as a first- and second-line treatment for patients with locally advanced or metastatic urothelial cancer. The FDA is scheduled to make a final decision on both applications on or before June 14, 2017.
The frontline application, which is for cisplatin-ineligible patients, is based on data from the open-label phase II KEYNOTE-052 study. In the first 100 patients enrolled in the study, the objective response rate with pembrolizumab was 24%, which included a 6% complete response rate. After a median follow-up of 8 months, the median duration of response was not yet reached (range, 1.4+ to 9.8+ months), and 83% of patients responded to therapy for ≥6 months.
The second-line application, which is for patients who progress following platinum-containing chemotherapy, is based on data from the phase III KEYNOTE-045 study, in which single-agent pembrolizumab reduced the risk of death by 27% compared with chemotherapy in patients with advanced urothelial carcinoma whose disease progressed after prior treatment. The median overall survival for patients receiving pembrolizumab was 10.3 months (95% CI, 8.0-11.8 months) compared with 7.4 months (95% CI, 6.1-8.3 months) for those who received a chemotherapy regimen. The difference resulted in a hazard ratio of 0.73 (95% CI, 0.59-0.91 months). The survival benefit was observed regardless of PD-L1 expression status.
See more: http://www.onclive.com/web-exclusives/fda-grants-priority-review-to-frontline-pembrolizumab-for-urothelial-carcinoma and http://www.onclive.com/web-exclusives/fda-grants-pembrolizumab-priority-review-in-secondline-bladder-cancer
2017 European Cancer Congress
The 2017 European Cancer Congress was recently held in Amsterdam. Findings from one study presented at the meeting showed that an immunohistochemistry analysis of a large patient population demonstrated that several subtypes of difficult-to-treat sarcomas may respond to treatment with PD-1 pathway inhibiting immunotherapies.
Another study showed that pembrolizumab (Keytruda) provided durable activity for previously treated patients with mucosal melanoma. Here’s more http://www.onclive.com/web-exclusives/pembrolizumab-demonstrates-durable-responses-in-rare-subtype-of-melanoma And in a third study of note, ribociclib demonstrated similar clinical benefits and safety profiles for both elderly and younger patients with HR+/HER2- advanced breast cancer. These data point to a shift in paradigm for the future management of these patients, from the current standard of care, letrozole, to a combination regimen of letrozole plus ribociclib.
Frontline Pembrolizumab Approved in Europe for PD-L1+ NSCLC
The European Commission has expanded the indication for pembrolizumab (Keytruda) to include the frontline treatment of patients with metastatic non—small cell lung cancer (NSCLC) that expresses PD-L1 on ≥50% of cells and does not harbor an EGFR or ALK mutation. The approval was based on data from phase III KEYNOTE-024 trial, and followed a positive opinion from the Committee for Medicinal Products for Human Use, which was granted in December 2016.
In the pivotal trial, frontline pembrolizumab reduced the risk of death by 40% and improved progression-free survival (PFS) by 4.3 months compared with standard doublet chemotherapy for patients with metastatic PD-L1—positive NSCLC. The estimated 6-month overall survival (OS) rate was 80.2% with pembrolizumab versus 72.4% with chemotherapy (HR, 0.60; 95% CI, 0.41-0.89; P = .005). The median PFS was 10.3 months with pembrolizumab versus 6.0 months with chemotherapy (HR, 0.50; 95% CI, 0.37-0.68; P <.001). The 6-month PFS rate was 62.1% in the pembrolizumab arm versus 50.3% with chemotherapy.
This benefit remained consistent across subgroups. At the time of the analysis, median OS had not yet been reached. The objective response rate with pembrolizumab was 44.8% compared with 27.8% with chemotherapy. The duration of response was not reached in the immunotherapy arm versus 6.3 months with chemotherapy.
Immunotherapy 2.0 is ASCO's Cancer Advance of the Year
With 5 agents approved in 2016 alone, immunotherapy continues to revolutionize the treatment paradigms for a number of different cancers. Recognizing the impact that these agents have had over the past year, the American Society of Clinical Oncology (ASCO) named “Immunotherapy 2.0” as the Advance of the Year in its Clinical Cancer Advances 2017: ASCO’s Annual Report on Progress Against Cancer, which is published in the Journal of Clinical Oncology.
“In less than a decade, immunotherapy has gone from being considered a promising theoretical treatment to one that has become a standard of care that is helping extend or improve the lives of thousands of patients,” Daniel F. Hayes, MD, president of ASCO, said in a statement.