February 28, 2018 - Episode 1

FDA Approvals in Breast Cancer and Bladder Cancer, and Phase I/II Data With Larotrectinib


FDA approvals in breast cancer and bladder cancer, promising findings in a phase I/II biomarker-driven trial, and European regulatory updates in multiple myeloma and ovarian cancer.

Welcome to OncLive News Network! I'm Gina Columbus.

The FDA has approved abemaciclib for use in combination with an aromatase inhibitor for the frontline treatment of postmenopausal women with hormone receptor-positive, HER2-negative advanced or metastatic breast cancer.

The approval of the CDK4/6 inhibitor was based on data from the phase III MONARCH 3 trial, in which the addition of abemaciclib to anastrozole or letrozole reduced the risk of progression or death by 46% versus the nonsteroidal aromatase inhibitor alone for previously untreated patients with HER2-negative, HR-positive advanced disease.

Results showed that the median progression-free survival was 28.2 months in the abemaciclib arm versus 14.8 months with the NSAI alone. In those with measurable disease, the objective response rate was 55.4% with the CDK4/6 inhibitor and 40.2% in the control arm.

The ORR among patients with measurable disease receiving abemaciclib included a complete response rate of 3.4% and a partial response rate of 52.1%. The 40.2% ORR in the control arm consisted of all partial responses. The median duration of response was 27.4 months for the abemaciclib arm compared with 17.5 months in the control arm.


In bladder cancer, the FDA granted an approval to a supplemental new drug application for Blue Light Cystoscopy with Cysview for surveillance of disease.

Photocure, the manufacturer of Cysview, sought to expand the label to include use in the outpatient setting to detect the recurrence of bladder cancer using a flexible cystoscope. The FDA had granted this a priority review designation in October 2017. Additionally, the sNDA included a request for repetitive use of Cysview, which was also approved.

The bladder imaging agent was initially approved in the United States in 2010 and is currently indicated for use for detection of nonmuscle-invasive bladder cancer for patients who, based on prior cystoscopy results, have or are suspected to have lesions.

The expanded approval was based on positive data from a phase III study that tested Cysview with the flexible scope system. Results showed that 20.6% of cases of bladder cancer recurrence would have been missed had Cysview not been used. Additionally, 9 out of 26 flat, more aggressive, high-grade lesions were diagnosed using confirmatory BLC with Cysview, and not with white light.


Updated findings for the novel pan-TRK inhibitor larotrectinib showed that it induced durable responses in patients with TRK fusion-positive solid tumors enrolled across a phase I adult trial, the phase II NAVIGATE trial, and the phase I/II SCOUT pediatric trial.

Among 55 evaluable patients, the objective response rate was 75% by independent review and 80% by investigator assessment. In the independent assessment, there were 7 complete responses, 34 partial responses, and 5 patients with stable disease.

At 1 year, 71% of responses were ongoing and more than half of patients remained progression-free. The median duration of response had not been reached after a median follow-up of 8.3 months. The same was true for median progression-free survival after a median follow-up of 9.9 months.

TRK gene fusions appear across a wide range of tumors-including breast and colorectal cancer, infantile fibrosarcoma, lung cancer, melanoma, and various sarcomas-and lead to uncontrolled TRK signaling and tumor growth.

Loxo Oncology and Bayer, the companies developing larotrectinib, filed a rolling new drug application with the FDA for the treatment of adult and pediatric patients based on these findings in December 2017. Bayer expects to file a marketing authorization application with the European Union this year.


In multiple myeloma, the European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of denosumab for the prevention of skeletal-related events.

The CHMP recommendation is based on findings from the phase III 482 study, in which denosumab demonstrated noninferiority to zoledronic acid at delaying the time to the first SRE in patients with multiple myeloma. Based on these findings, the FDA approved denosumab in this setting in January 2018.

The median time to first on-study SRE was similar between the denosumab arm and zoledronic acid group. The median overall survival was 49.5 months with denosumab versus not-estimable with zoledronic acid. Median progression-free survival favored the denosumab arm at 46.1 months versus 35.4 months for the zoledronic acid arm.


The European Medicines Agency's Committee for Medicinal Products for Human Use has recommended approval of olaparib tablets as a maintenance therapy for patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer, who are in a complete or partial response to platinum-based chemotherapy, regardless of BRCA status.

A capsule formulation of olaparib is currently approved in the European Union for use in this setting; however, its use is limited to patients with BRCA mutations. AstraZeneca and Merck, the developers of olaparib, noted in a news release that the new formulation will lower dosing from 8 capsules twice daily to 2 tablets twice daily.

The CHMP opinion is based on data from the phase III SOLO2 trial and the phase II Study 19 trial. In SOLO2, maintenance olaparib tablets showed a 70% reduction in the risk of progression or death versus placebo for patients with platinum-sensitive, relapsed, BRCA-mutant ovarian cancer. In Study 19, the risk of progression or death was reduced by 65% with maintenance olaparib versus placebo for women with ovarian cancer, regardless of BRCA status.

Based on these findings, the FDA approved olaparib in this setting in August 2017. The positive CHMP opinion will now be sent to the European Commission for a final regulatory decision.


This week, we sat down with Dr Ghassan K. Abou-Alfa of Memorial Sloan Kettering Cancer Center to discuss immunotherapy after treatment with sorafenib in patients with hepatocellular carcinoma.

That's all for today.

Thank you for watching OncLive News Network! I'm Gina Columbus.