FDA approves bevacizumab for ovarian cancer and pembrolizumab for large B-cell lymphoma cancer
Bevacizumab for Ovarian Cancer
On June 13, 2018, the Food and Drug Administration approved bevacizumab (Avastin®, Genentech, Inc.) for patients with epithelial ovarian, fallopian tube, or primary peritoneal cancer in combination with carboplatin and paclitaxel, followed by single-agent bevacizumab, for stage III or IV disease after initial surgical resection.
Approval was based on GOG-0218 (NCT00262847), a multicenter, randomized, double-blind, placebo-controlled, three-arm study evaluating the addition of bevacizumab to carboplatin and paclitaxel for patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection. Patients (n=1,873) were randomized (1:1:1) to carboplatin plus paclitaxel without bevacizumab, carboplatin plus paclitaxel with bevacizumab for up to six cycles, or carboplatin plus paclitaxel with bevacizumab for six cycles followed by single-agent bevacizumab for up to 16 additional doses. Bevacizumab was administered at 15 mg/kg intravenously every three weeks. On this trial, 1,215 patients received at least one bevacizumab dose.
The primary efficacy outcome was investigator-assessed progression-free survival (PFS); overall survival (OS) was a secondary outcome. The estimated median PFS was 18.2 months for patients receiving bevacizumab with chemotherapy followed by single-agent bevacizumab (HR 0.62; 95% CI: 0.52, 0.75; p<0.0001). For those receiving bevacizumab with chemotherapy without single-agent bevacizumab, the estimated median PFS was 12.8 months (HR 0.83; 95% CI: 0.70, 0.98; not significant). For patients receiving chemotherapy without bevacizumab, the estimated median PFS was 12.0 months. Estimated median OS was 43.8 months in the bevacizumab with chemotherapy followed by bevacizumab compared to 40.6 months in the chemotherapy alone arm (HR 0.89; 95% CI: 0.76, 1.05).
Adverse reactions occurring at higher incidence (at least 5%) of patients receiving bevacizumab in GOG-0218 were diarrhea, nausea, stomatitis, fatigue, arthralgia, muscular weakness, pain in extremity, dysarthria, headache, dyspnea, epistaxis, nasal mucosal disorder, and hypertension. Grade 3-4 adverse reactions occurring at a higher incidence (≥2%) in either of the bevacizumab arms versus the control arm were fatigue, hypertension, platelet count decreased, and white blood cell count decreased.
The recommended bevacizumab dose for stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer following initial surgical resection is 15 mg/kg every 3 weeks with carboplatin and paclitaxel for up to 6 cycles, followed by 15 mg/kg every 3 weeks as a single- agent, for a total of up to 22 cycles. View full prescribing information for Avastin.
FDA granted bevacizumab orphan product designation for this indication. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Pembrolizumab for Lymphoma
On June 13, 2018, the Food and Drug Administration granted accelerated approval to pembrolizumab (Keytruda®, Merck) for the treatment of adult and pediatric patients with refractory primary mediastinal large B-cell lymphoma (PMBCL), or who have relapsed after two or more prior lines of therapy.
Approval was based on data from 53 patients with relapsed or refractory PMBCL enrolled in a multicenter, open-label, single-arm trial, KEYNOTE 170 (NCT02576990). Patients were treated with pembrolizumab 200 mg intravenously every 3 weeks until unacceptable toxicity or documented disease progression, or for up to 24 months for patients who did not progress. The overall response rate was 45% (95% CI: 32, 60), including 11% complete responses and 34% partial responses. The median duration of response was not reached within the follow-up period (median 9.7 months). The median time to first objective response was 2.8 months; pembrolizumab is not recommended for treatment of patients with PMBCL who require urgent cytoreductive therapy.
The most common adverse reactions in ≥10% of patients with PMBCL treated in KEYNOTE-170 were musculoskeletal pain, upper respiratory tract infection, pyrexia, fatigue, cough, dyspnea, diarrhea, abdominal pain, nausea, arrhythmia, and headache. Pembrolizumab was discontinued or interrupted due to adverse reactions in 8% and 15% of patients, respectively. Twenty-five percent of patients had an adverse reaction requiring systemic corticosteroid therapy. Serious adverse reactions occurred in 26% of patients.
The recommended pembrolizumab dose for treatment of adults with PMBCL is 200 mg every 3 weeks. The recommended dose in pediatric patients is 2 mg/kg (up to a maximum of 200 mg) every three weeks. View full prescribing information for Keytruda.
FDA granted this application priority review. Pembrolizumab also received orphan product designation and breakthrough therapy designation for the PMBCL indication. This indication is approved under accelerated approval based on tumor response rate and durability of response. Continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. A description of FDA expedited programs is in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System or by calling 1-800-FDA-1088.
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