FDA Update

On September 22, 2017, the U.S. Food and Drug Administration (FDA) granted accelerated approval to pembrolizumab (Ketruda®) for patients with recurrent locally advanced or metastatic, gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 as determined by an FDA-approved test. Patients must have had disease progression on or after two or more prior systemic therapies, including fluoropyrimidine- and platinum-containing chemotherapy and, if appropriate, HER2/neu-targeted therapy.

Approval is based on the results of KEYNOTE‑059 (NCT02335411), an open-label, multicenter, non-comparative, multicohort trial that enrolled 259 patients with gastric or gastroesophageal junction adenocarcinoma. Among the 259 patients, 55% (n=143) had tumors expressing PD-L1 and either microsatellite stable (MSS), or undetermined microsatellite instability (MSI) or mismatch repair (MMR) status.

PD-L1 expression was evaluated by the PD-L1 IHC 22C3 pharmDx Kit (Dako) and PD-L1 positivity was based on a combined positive score (CPS) ≥ 1. CPS is determined by the number of PD-L1 staining cells (tumor cells, lymphocytes, macrophages) divided by total number of tumor cells evaluated, multiplied by 100.

For the 143 patients with tumors expressing PD-L1 and who were either MSS or had unknown MSI or dMMR status, the objective response rate was 13.3% (95% CI: 8.2, 20.0); 1.4% had complete responses and 11.9% had partial responses. Among the 19 responding patients, the response duration ranged from 2.8+ to 19.4+ months, with 11 patients (58%) having response durations of 6 months or longer and 5 patients (26%) having response durations of 12 months or longer.

Among the 259 patients enrolled in KEYNOTE‑059, 7 (3%) had tumors that were determined to be MSI-high. Responses were observed in 4 of these 7 patients (ORR 57%), with one complete response. The response duration ranged from 5.3+ to 14.1+ months.

Adverse reactions occurring in patients with gastric cancer were similar to those presently described in product labelling. The most common adverse reactions are fatigue, musculoskeletal pain, decreased appetite, pruritus, diarrhea, nausea, rash, pyrexia, cough, dyspnea, and constipation. Pembrolizumab is associated with immune-mediated side effects, including pneumonitis, colitis, hepatitis, endocrinopathies, and nephritis.

The recommended pembrolizumab dose for gastric cancer is 200 mg administered as an intravenous infusion over 30 minutes every 3 weeks until disease progression, unacceptable toxicity, or up to 24 months in patients without disease progression.

Today, FDA also approved the PD-L1 IHC 22C3 pharmDx (Dako), to select patients with gastric cancer for treatment with pembrolizumab. If PD-L1 expression is not detected in an archival gastric cancer specimen, FDA recommends assessing the feasibility of a fresh tumor biopsy. Information on FDA-approved tests for PD-L1 expression in NSCLC or in gastric cancer is available.

Full prescribing information is available.

FDA granted pembrolizumab priority review for this indication. As a condition of accelerated approval, further studies are required. 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 by completing a form online, by faxing (1-800-FDA-0178) or mailing the postage-paid address form provided online, or by telephone (1-800-FDA-1088).

Follow the Oncology Center of Excellence on Twitter @FDAOncology.

Check out recent approvals at the OCE’s podcast, Drug Information Soundcast in Clinical Oncology (DISCO).

In collaboration with the FDA and as a service to our members, ONS provides updates on recent FDA approvals and other important FDA actions (e.g., updated safety information, new prescribing information) pertaining to therapies for patients with cancer. This allows the agency to inform oncologists and professionals in oncology-related fields in a timely manner. Included in the FDA updates is a link to the product label or to other sites for additional relevant clinical information. In supplying this information, ONS does not endorse any product or therapy and does not take any position on the safety or efficacy of the product or therapy described.

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