FDA News - September 2018

TON - September 2018, Vol 11, No 4 - FDA Approvals, News & Updates
This section provides a brief overview of new cancer drugs or new indications approved by the FDA between June 8 and June 13, 2018.

Venclexta Indicated for CLL or SLL, Alone or in Combination with Rituxan

Venclexta Indicated for CLL or SLL, Alone or in Combination with Rituxan

On June 8, 2018, the FDA approved venetoclax (Venclexta; AbbVie/Genentech) for patients with chronic lymphocytic leukemia (CLL) or with small lymphocytic lymphoma, regardless of 17p deletion, who received previous therapy, as monotherapy or in combination with rituximab (Rituxan; Genentech).

The new indication for venetoclax plus rituximab was based on MURANO, a multicenter, open-­label clinical trial of 389 patients with CLL who received ≥1 previous therapies. Patients received venetoclax plus rituximab or bendamustine plus rituximab. Patients in the venetoclax arm received venetoclax 400 mg once daily for 2 years after completing a 5-week ramp-up of venetoclax. Rituximab was added on day 1 of each of the 6 cycles of 28-day length. Patients in the bendamustine plus rituximab arm received the combination for 6 cycles of 28-day length (bendamustine on days 1-2 of each cycle, and rituximab on day 1 of each cycle).

At 23 months, the median progression-free survival was not reached in the venetoclax arm and was 18.1 months in the bendamustine arm (P <.0001). The overall response rate was 92% in the venetoclax plus rituximab arm versus 72% in the bendamustine plus rituximab arm.

Grade 3 or 4 neutropenia was 64% in the venetoclax plus rituximab arm; grade 4 neutropenia was 31%. Serious adverse events (46%) and serious infections (21%) were also reported. The most common (9%) serious infection was pneumonia. Tumor lysis syndrome is a significant risk associated with venetoclax.

Keytruda Receives 2 New Indications: Metastatic Cervical Cancer and Relapsed Mediastinal Large B-Cell Lymphoma

Keytruda Receives 2 New Indications: Metastatic Cervical Cancer and Relapsed Mediastinal Large B-Cell Lymphoma

On June 12, 2018, the FDA granted accelerated approval to pembrolizumab (Keytruda; Merck) for patients with recurrent or metastatic cervical cancer that progressed during or after chemotherapy and whose tumors express PD-L1, as determined by an FDA-approved test. Concurrently, the FDA approved the PD-L1 IHC 22C3 pharmDx kit as a companion diagnostic test for determining the PD-L1 status in this patient population.

This approval was based on 98 patients in the KEYNOTE-158 study who had recurrent or metastatic cervical cancer expressing PD-L1, as was determined by the PD-L1 IHC 22C3 pharmDx test. At a median of 11.7-month follow-up, the overall response rate was 14.3% among 77 patients whose tumors expressed PD-L1; of these responses, 2.6% were complete responses and 11.7% were partial responses.

Based on 11 patients who responded to treatment, the median duration of response was not reached at the time of this approval; the duration of response was ≥6 months in 91% of the patients. No responses were seen in patients without PD-L1 expression.

Serious adverse reactions were reported in 39% of patients, and pembroliz­umab was discontinued in 8% of the patients because of adverse reactions.

A day later, on June 13, 2018, the FDA accelerated the approval of pembrolizumab for adult and pediatric patients with relapsed or refractory primary mediastinal large B-cell lymphoma (PMBCL). The FDA granted pembrolizumab orphan drug designation and breakthrough therapy designation for this indication.

This approval was based on results from the KEYNOTE-170 clinical trial of 53 patients with relapsed or refractory PMBCL. Patients received intravenous pembrolizumab 200 mg every 3 weeks for up to 2 years, or until disease progression or unacceptable toxicity.

The overall response rate was 45%, with 11% complete responses and 34% partial responses. In the 9.7-month follow-up, the median duration of response was not reached. Pembrolizu­mab is not recommended for patients with PMBCL for whom cytoreductive therapy is crucial.

Adverse events led to pembroliz­umab discontinuation (8%) or in­terruption (15%), and systemic corticosteroid therapy was required in 25% of patients who had an adverse reaction. Serious adverse events were reported in 26% of patients.

Bevacizumab plus Chemotherapy Approved for Several Types of Ovarian Cancer

Bevacizumab plus Chemotherapy Approved for Several Types of Ovarian Cancer

On June 13, 2018, the FDA approved bevacizumab (Avastin; Genentech), in combination with carboplatin and paclitaxel, for the treatment of patients with resected, stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer, to be followed with beva­cizumab monotherapy. Bevacizumab received orphan drug designation for this indication.

This approval was based on a multicenter, double-blind, placebo-­controlled clinical trial of 1873 ­patients with stage III or IV epithelial ovarian, fallopian tube, or primary peritoneal cancer who had initial surgical resection. Patients were randomized to carboplatin plus paclitaxel; carboplatin plus paclitaxel with bevacizumab (for up to 6 cycles); or carboplatin plus pac­litaxel with bevacizumab for 6 cycles, followed by bevacizumab monotherapy for up to 16 additional doses. Bevaciz­umab was administered intravenously every 3 weeks. A total of 1215 patients received ≥1 bevacizumab doses.

In patients receiving bevacizumab plus chemotherapy followed by bevaciz­umab, the median progression-free survival (PFS) was 18.2 months compared with 12.8 months for those receiving bevacizumab plus chemotherapy but no follow-up with bevacizumab monotherapy. The ­median PFS was 12 months with chemotherapy alone. The estimated median overall survival for the bevacizumab plus chemotherapy followed by bevacizumab arm was 43.8 months versus 40.6 months in the chemotherapy alone arm.

The most common (≥2%) grade 3 or 4 adverse events with bevacizumab were fatigue, hypertension, thrombocytopenia, and leukopenia.

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Last modified: September 26, 2018