FDA Drug Approvals Highlight Oncology News Roundup

Top news of the week in cancer drug development.

Second-Line MM-398 Approved for Pancreatic Cancer

The FDA has approved MM-398 (irinotecan liposome injection; Onivyde) in combination with 5-fluorouracil and leucovorin as a treatment for patients with metastatic pancreatic cancer following prior administration of a gemcitabine-based regimen, based on data from the phase III NAPOLI-1 trial.

In the combination arm, the median OS was 6.1 months compared with 4.2 months with 5-FU and leucovorin alone (HR, 0.57; P = .0009). The median progression-free survival was 3.1 months for the combination compared with 1.5 months with the control (HR, 0.56; P = .0001).

At 12 weeks, 57% of patients treated with the combination were alive and progression-free compared with 26% with 5-FU and leucovorin alone. The objective response rate by RECIST v1.1 criteria was 16% versus 1%, for the combination and control, respectively (P <.001).

The treatment was approved along with a boxed warning regarding severe neutropenia and diarrhea, which is a common adverse event associated with irinotecan-based therapy. Additionally, the FDA noted that MM-398 should not be used a monotherapy, since there were more AEs associated with single-agent MM-398 versus the combo (which is likely related to leucovorin).

See more at: http://www.onclive.com/web-exclusives/fda-approves-mm-398-regimen-for-metastatic-pancreatic-cancer

FDA Approves Trabectedin for Soft Tissue Sarcoma

The FDA approved trabectedin for the treatment of patients with unresectable or metastatic liposarcoma and leiomyosarcoma following previous treatment with chemotherapy, including an anthracycline.

The approval was based on results from the phase III ET743-SAR-3007 trial, in which trabectedin reduced the risk of disease progression by 45% versus dacarbazine in patients with advanced soft tissue sarcoma.

There was also a slight survival trend with trabectedin, but the results were not significant. After 329 events for the endpoint of progression-free survival, patients receiving trabectedin had a statistically significant reduction in the risk of disease progression, with a median PFS of 4.2 months versus 1.5 months with dacarbazine (HR, 0.55; P <.001).

The 3-month PFS rates were 56% versus 34% for the two arms, respectively, and the 6-month PFS rates were 37% versus 14%. The objective response rate was 9.9% with trabectedin and 6.9% with dacarbazine.

The clinical benefit rates (ORR plus stable disease ≥18 weeks) were 34.2% and 18.5% in the two arms, respectively (P = .0002). The median OS was 13.7 months with trabectedin versus 13.1 months with dacarbazine (HR, 0.93; P = .49), according to the FDA.

See more at: http://www.onclive.com/web-exclusives/fda-approves-trabectedin-in-soft-tissue-sarcoma

Pembrolizumab Improves OS in NSCLC

Pembrolizumab extended overall survival versus docetaxel for patients with non—small cell lung cancer in the phase II/III KEYNOTE-010 trial, building on data that led to an accelerated approval for the PD-1 inhibitor earlier this month. Merck, the company developing the drug, plans to submit data from the trial to the FDA for a full regulatory approval by the end of the year.

For the accelerated approval, pembrolizumab was approved along with a companion diagnostic, the PD-L1 IHC 22C3 pharmDx test, and is indicated for patients who progress on or after platinum-containing chemotherapy or EGFR-or ALK-targeted agents in patients harboring those mutations.

This decision was based on the phase I KEYNOTE-001 trial, in which the overall response rate with the drug was 41% among a subgroup of 61 patients with pretreated PD-L1—positive advanced NSCLC as determined by the 22C3 pharmDx diagnostic test. For the KEYNOTE-010 study, pembrolizumab improved overall survival versus docetaxel in the standard and higher-dose arms, as well as both in the overall study population and in the strongly PD-L1–positive subgroup.

PFS was also improved with both doses of pembrolizumab versus chemotherapy in the high PD-L1 expressers. Among patients with PD-L1 expression <50%, PFS was improved with pembrolizumab, but the difference was not statistically significant. Data from the study were not yet made available.

See more at: http://www.onclive.com/web-exclusives/pembrolizumab-improves-survival-versus-docetaxel-in-pd-l1-nsclc

Rolling Submission Initiated for Cabozantinib in RCC

Rolling submission of a new drug application for cabozantinib has been initiated for patients with advanced renal cell carcinoma who have received one prior therapy.

The application for cabozantinib was based on findings from the phase III METEOR trial, which demonstrated a 42% reduction in the risk of progression or death for cabozantinib versus everolimus in patients with advanced RCC.

Median PFS with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; P <.001). By investigator assessment, the median PFS was 7.4 months with cabozantinib and 5.3 months with everolimus (HR, 0.60; P <.001).

At the interim analysis of the full study population, a trend toward improvement in overall survival was observed; however, this did not pass a high bar for statistical significance (HR, 0.67; P = .005). Rolling submission of an NDA is allowed as part of a breakthrough therapy designation received by the multikinase inhibitor in August 2015.

Once fully submitted, the FDA will review the application within 60 days, at which point the agency will assign a review deadline under the Prescription Drug User Fee Act. Exelixis anticipates that all data will be submitted by the end of the year.

See more at: http://www.onclive.com/web-exclusives/fda-approval-sought-for-cabozantinib-in-advanced-rcc

American Cancer Society Updates Breast Cancer Screening Guideline

Recently, the American Cancer Society issued a controversial update to its breast cancer screening guideline, which now recommends that women at an average risk of breast cancer should wait to undergo annual screening mammography until they reach the age of 45.

Additionally, after the age of 55, the guideline recommends transitioning mammography to every other year. Prior ACS recommendations, which were formulated in 2003, recommended that annual screening should begin at age 40 and should continue indefinitely.

In the updated guideline, screening for women age 40 to 44 is listed as a personal choice rather than a strong recommendation. For women older than 55 years, annual screening is also listed as a personal choice, in favor of biennial exams.

Additionally, the new guideline did not place a maximum age on screening for healthy individuals, as long as life expectancy was greater than 10 years. Although the ACS guideline calls for less screening versus the previous rendition, the ACS opinion still promotes more screening than the USPSTF recommendation.

In the USPSTF guideline, screening is recommended every 2 years for those between the ages of 50 and 74 and is recommended against for those aged 40 to 49.

See more at: http://www.onclive.com/web-exclusives/american-cancer-society-updates-breast-cancer-screening-guideline

FDA Issues Complete Response Letter for CE-Melphalan

The FDA issued a complete response letter to Spectrum Pharmaceuticals, informing the company that its new drug application for the use of Captisol-enabled melphalan in multiple myeloma will not be approved in its current form.

Spectrum was seeking marketing approval for CE- melphalan for the treatment of patients with multiple myeloma prior to autologous stem cell transplantation, as well as for the palliative treatment of patients with myeloma for whom oral therapy is not appropriate.

The NDA was based on results from a multicenter, open-label phase IIb study in which the overall response rate to CE melphalan was 95% among 61 patients, with all patients having successful myeloablation (median 5 days post-AHCT) and subsequent neutrophil and platelet engraftment (median, 12-13 days post-AHCT) with no mortality at day 100.

The Chairman and CEO of Spectrum, Rajesh C. Shrotriya, MD, said the company would work "swiftly" to address the comments provided by the FDA in the complete response letter.

See more at: http://www.onclive.com/web-exclusives/fda-issues-complete-response-letter-for-ce-melphalan-in-myeloma