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FDA Updates

FDA News Highlighting the Latest Cancer Treatments

doi: 10.1097/01.COT.0000534149.84204.a5
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Pembrolizumab Granted Priority Review for Cervical Cancer


The FDA has accepted a new supplemental Biologics License Application and granted Priority Review for pembrolizumab, an anti-PD-1 therapy. The application is seeking approval for pembrolizumab as a treatment for patients with advanced cervical cancer with disease progression on or after chemotherapy.

This is the first filing acceptance and Priority Review granted for an anti-PD-1 therapy in cervical cancer and the 14th regulatory submission accepted by the FDA for pembrolizumab. The FDA has set a PDUFA, or target action, date of June 28, 2018.

The application, which is seeking accelerated approval for this new indication, is based in part on data from the phase II KEYNOTE-158 trial. It is an ongoing global, open-label, non-randomized, multi-cohort, multi-center study evaluating pembrolizumab in patients with multiple types of advanced solid tumors—including cervical cancer—that have progressed on standard of care therapy.

Initial data was presented at the 2017 ASCO Annual Meeting (Abstract 5514). Investigators reported that, among the first 47 patients with advanced cervical cancer who enrolled, ORR was 17 percent (95% CI, 8-31%), with three confirmed and five unconfirmed responses. Additionally, 41 (87%) patients had PD-L1-positive tumors, and ORR was independent of PD-L1 status. Among the 15 patients who had ≥27 weeks of follow-up, ORR was 27 percent (95% CI 8-55%), with three confirmed responses and one unconfirmed response, according to study authors.

In 2017, approximately 12,820 cases of cervical cancer were diagnosed in the U.S. The 5-year survival rate of women with stage IV disease is an estimated 15-16 percent. Any woman can develop cervical cancer, but it is more commonly diagnosed in women between the ages of 35 and 44. While screenings and vaccinations have resulted in declining cervical cancer rates, the disease continues to affect women in the U.S. and throughout the world.

Rucaparib as Maintenance Treatment for Ovarian Cancer

The FDA has approved rucaparib tablets for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in a complete or partial response to platinum-based chemotherapy.

The FDA granted regular approval for rucaparib in this second, broader, and earlier-line indication on a priority review timeline based on positive data from the phase III ARIEL3 clinical trial. Biomarker testing is not required for patients to be prescribed rucaparib in this maintenance treatment indication.

In addition to granting rucaparib approval in this second indication, the FDA converted the approval of the initial treatment indication from accelerated to regular approval.

“Rucaparib provided statistically significant improvement in PFS versus placebo to all patients, regardless of BRCA mutation status,” said Robert L. Coleman, MD, Professor & Executive Director, Cancer Network Research; and the Ann Rife Cox Chair in Gynecology, Department of Gynecologic Oncology and Reproductive Medicine at University of Texas MD Anderson Cancer Center in Houston, as well as one of the principal investigators in the ARIEL3 clinical trial program. “Both the efficacy and safety results from the ARIEL3 study reinforce the important role of rucaparib in the treatment of recurrent ovarian cancer and expands the treatment options for patients and physicians battling this disease.”

On Feb. 28, 2018, rucaparib was added to the National Comprehensive Cancer Network (NCCN) Clinical Practice Guidelines in Oncology Ovarian Cancer as maintenance therapy for patients with platinum-sensitive epithelial ovarian, fallopian tube, and primary peritoneal cancer who are in partial or complete response after completion of two or more lines of platinum-based therapy. The NCCN designated rucaparib as a category 2A treatment.

In December 2017, FDA accepted the rucaparib supplemental New Drug Application application and granted priority review status. Priority review designation is granted to proposed medicines the FDA has determined have the potential, if approved, to offer a significant improvement in the safety or effectiveness for the treatment, prevention, or diagnosis of a serious condition when compared to standard applications. The rucaparib maintenance treatment approval is based on positive results from the ARIEL3 study, which evaluated rucaparib in the ovarian cancer maintenance-treatment setting among three populations: 1) BRCA mutant (BRCAmut+); 2) HRD positive inclusive of BRCAmut+; and, 3) all patients treated in ARIEL3. The study enrolled a total of 564 patients.

ARIEL3 successfully achieved both its primary and key secondary endpoints, extending investigator assessed progression-free survival versus placebo in all patients treated, regardless of BRCA status.

Topline results from the ARIEL3 clinical trial were released in June 2017. Additional data from the trial were presented at the 2017 ESMO Congress and subsequently published in The Lancet.

“The FDA approval of rucaparib in the maintenance-treatment setting is an important milestone for physicians and their patients with recurrent ovarian cancer because it offers them greater flexibility to use this novel PARP inhibitor, which has demonstrated significant clinical efficacy and has been well-received in practice,” said Jonathan Ledermann, MD, Professor of Medical Oncology and Clinical Director, UCL Cancer Institute, University College London, as well as principal investigator for the ARIEL3 study. “This will enable physicians to offer rucaparib to more women with platinum-sensitive, recurrent ovarian cancer.”

“Tens of thousands of women will battle ovarian cancer every year,” said David Barley, Chief Executive Officer, National Ovarian Cancer Coalition. “We need therapies that provide clinically meaningful improvements in reducing the risk of disease progression among women with recurrent disease.”

The safety evaluation of rucaparib 600 mg twice daily as monotherapy for maintenance treatment is based on data from 561 patients with recurrent ovarian cancer treated in the ARIEL3 trial. The safety and tolerability observed in this study were consistent with the previous rucaparib studies. The most common adverse reactions (greater than or equal to 20% of patients; CTCAE grade 1-4) were nausea, fatigue/asthenia, abdominal pain/distention, rash, dysgeusia, anemia, AST/ALT elevation, constipation, vomiting, diarrhea, thrombocytopenia, nasopharyngitis/upper respiratory tract infection, stomatitis, decreased appetite, and neutropenia.

The most common laboratory abnormalities (greater than or equal to 25% of patients; CTCAE grade 1-4) were increase in creatinine, decrease in hemoglobin, increase in cholesterol, increase in ALT, increase in AST, decrease in platelets, decrease in leukocytes, decrease in neutrophils, increase in alkaline phosphatase, and decrease in lymphocytes. The majority of adverse reactions and laboratory abnormalities were grade 1-2.

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