FDA News

Pembrolizumab approved for two solid tumor indications

The FDA approved pembrolizumab for patients with metastatic small cell lung cancer that progressed after platinum-based chemotherapy and at least one other prior line of therapy.

The FDA also approved pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy, as monotherapy for certain patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus.

Small cell lung cancer

The FDA granted pembrolizumab accelerated approval for smell cell lung cancer based on tumor response rate and durability of response observed in KEYNOTE-158 and KEYNOTE-028.

Those trials included 83 patients with small cell lung cancer, 64% of whom had received two prior lines of therapy and 36% of whom had received three or more lines of therapy. Sixty percent of patients previously received thoracic radiotherapy and 51% had received radiotherapy to the brain.

Patients received 200 mg IV pembrolizumab every 3 weeks (n = 64) or 10 mg/kg IV every 2 weeks (n = 19) until documented disease progression, unacceptable toxicity or for a maximum of 24 months.

Objective response rate and duration of response served as the primary efficacy outcome measures.

Results showed an ORR of 19% (95% CI, 11-29), which included a 2% complete response rate and 17% partial response rate.

Responses ranged from 4.1 to 35.8+ months, with 94% of responders experiencing a duration of response of 6 months or longer. For 56% of these patients, response exceeded 18 months.

“Small cell lung cancer, which accounts for 10% to 15% of all lung cancers, is often diagnosed at an advanced stage, where the prognosis is very poor, and there have historically been limited treatment options,” Patrick Ott, MD, PhD, clinical director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute, said in a press release. “The approval of Keytruda in small cell lung cancer provides an additional treatment option for patients.”

Esophageal cancer

FDA’s approval of pembrolizumab for esophageal cancer applies to patients whose tumors express PD-L1 — with a combined positive score of 10 or higher — as determined by an FDA-approved test, and who experienced disease progression after one or more previous lines of systemic therapy.

The FDA based the approval on results from the randomized controlled KEYNOTE-181 trial, which included 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced disease.

Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks or investigator’s choice of IV chemotherapy with paclitaxel, docetaxel or irinotecan. Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

OS among three groups — patients with esophageal squamous cell carcinoma, those whose tumors express PD-L1, and all randomly assigned patients — served as the key efficacy outcome.

Researchers reported HRs for OS of 0.77 (95% CI, 0.63-0.96) among patients with esophageal squamous cell carcinoma; 0.7 (95% CI, 0.52-0.94) among patients whose tumors met the defined PD-L1 expression threshold; and 0.89 (95% CI, 0.75-1.05) among all randomly assigned patients.

Among patients with esophageal squamous cell carcinoma who met the defined PD-L1 expression threshold, those assigned pembrolizumab achieved longer median OS (10.3 months vs. 6.7 months; HR = 0.64; 95% CI, 0.46-0.9) and median PFS (3.2 months vs. 2.3 months; HR = 0.66; 95% CI, 0.48-0.92).

A higher percentage of pembrolizumab-treated patients achieved response (22% vs. 7%), complete response (5% vs. 1%) and partial response (18% vs. 6%). Median duration of response was 9.3 months in the pembrolizumab group and 7.7 months in the chemotherapy group.

The FDA also considered data from the KEYNOTE-180 trial, a nonrandomized, open-label study that included 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease.

Thirty-five patients with esophageal squamous cell carcinoma expressed PD-L1 with a combined positive score of 10 or higher. Seven of these patients achieved response, equating to an ORR of 20%. The duration of response ranged from 4.2 months to more than 25.1 months. Five patients achieved responses that lasted 6 months or longer, and three patients achieved responses that lasted 12 months or longer.

The FDA approved pembrolizumab for patients with metastatic small cell lung cancer that progressed after platinum-based chemotherapy and at least one other prior line of therapy.

The FDA also approved pembrolizumab (Keytruda, Merck), an anti-PD-1 therapy, as monotherapy for certain patients with recurrent locally advanced or metastatic squamous cell carcinoma of the esophagus.

Small cell lung cancer

The FDA granted pembrolizumab accelerated approval for smell cell lung cancer based on tumor response rate and durability of response observed in KEYNOTE-158 and KEYNOTE-028.

Those trials included 83 patients with small cell lung cancer, 64% of whom had received two prior lines of therapy and 36% of whom had received three or more lines of therapy. Sixty percent of patients previously received thoracic radiotherapy and 51% had received radiotherapy to the brain.

Patients received 200 mg IV pembrolizumab every 3 weeks (n = 64) or 10 mg/kg IV every 2 weeks (n = 19) until documented disease progression, unacceptable toxicity or for a maximum of 24 months.

Objective response rate and duration of response served as the primary efficacy outcome measures.

Results showed an ORR of 19% (95% CI, 11-29), which included a 2% complete response rate and 17% partial response rate.

Responses ranged from 4.1 to 35.8+ months, with 94% of responders experiencing a duration of response of 6 months or longer. For 56% of these patients, response exceeded 18 months.

“Small cell lung cancer, which accounts for 10% to 15% of all lung cancers, is often diagnosed at an advanced stage, where the prognosis is very poor, and there have historically been limited treatment options,” Patrick Ott, MD, PhD, clinical director of the Center for Immuno-Oncology at Dana-Farber Cancer Institute, said in a press release. “The approval of Keytruda in small cell lung cancer provides an additional treatment option for patients.”

Esophageal cancer

FDA’s approval of pembrolizumab for esophageal cancer applies to patients whose tumors express PD-L1 — with a combined positive score of 10 or higher — as determined by an FDA-approved test, and who experienced disease progression after one or more previous lines of systemic therapy.

The FDA based the approval on results from the randomized controlled KEYNOTE-181 trial, which included 628 patients with recurrent locally advanced or metastatic esophageal cancer who progressed on or after one prior line of systemic treatment for advanced disease.

Researchers randomly assigned patients 1:1 to pembrolizumab 200 mg every 3 weeks or investigator’s choice of IV chemotherapy with paclitaxel, docetaxel or irinotecan. Treatment continued for up to 24 months, or until disease progression or unacceptable toxicity.

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OS among three groups — patients with esophageal squamous cell carcinoma, those whose tumors express PD-L1, and all randomly assigned patients — served as the key efficacy outcome.

Researchers reported HRs for OS of 0.77 (95% CI, 0.63-0.96) among patients with esophageal squamous cell carcinoma; 0.7 (95% CI, 0.52-0.94) among patients whose tumors met the defined PD-L1 expression threshold; and 0.89 (95% CI, 0.75-1.05) among all randomly assigned patients.

Among patients with esophageal squamous cell carcinoma who met the defined PD-L1 expression threshold, those assigned pembrolizumab achieved longer median OS (10.3 months vs. 6.7 months; HR = 0.64; 95% CI, 0.46-0.9) and median PFS (3.2 months vs. 2.3 months; HR = 0.66; 95% CI, 0.48-0.92).

A higher percentage of pembrolizumab-treated patients achieved response (22% vs. 7%), complete response (5% vs. 1%) and partial response (18% vs. 6%). Median duration of response was 9.3 months in the pembrolizumab group and 7.7 months in the chemotherapy group.

The FDA also considered data from the KEYNOTE-180 trial, a nonrandomized, open-label study that included 121 patients with locally advanced or metastatic esophageal cancer who progressed on or after at least two prior systemic treatments for advanced disease.

Thirty-five patients with esophageal squamous cell carcinoma expressed PD-L1 with a combined positive score of 10 or higher. Seven of these patients achieved response, equating to an ORR of 20%. The duration of response ranged from 4.2 months to more than 25.1 months. Five patients achieved responses that lasted 6 months or longer, and three patients achieved responses that lasted 12 months or longer.