In the Journals

Pembrolizumab safe, active in advanced cervical cancer

Pembrolizumab monotherapy appeared safe and induced durable antitumor responses in patients with advanced cervical cancer, according to interim results of the phase 2 KEYNOTE-158 study published in Journal of Clinical Oncology.

Based on these results, the FDA granted accelerated approval of pembrolizumab (Keytruda, Merck) for patients with advanced PD-L1-positive cervical cancer whose disease progressed during or after chemotherapy.

“Cervical cancer is the fourth leading cause of cancer-related mortality in women worldwide,” Hyun Cheol Chung, MD, PhD, professor at Yonsei University College of Medicine in Seoul, South Korea, and colleagues wrote. “In recent years, there has been a reduced incidence of cervical cancer in developed countries related to systematic screening, and we may expect the incidence and mortality rates to decline further if widespread vaccination against human papillomavirus is adopted.”

Chung and colleagues analyzed the safety and efficacy of pembrolizumab in a cohort of 98 patients (median age, 46 years; range, 24-75) with previously treated advanced cervical cancer. The cohort included 82 patients (83.7%) with PD-L1-positive tumors, 77 of whom had been treated for recurrent or metastatic cancer with one or more lines of chemotherapy.

Patients received 200 mg pembrolizumab every 3 weeks for 2 years or until disease progression, intolerable toxicity, or physician or patient decision to withdraw. Imaging of the tumor occurred every 9 weeks for the first year and every 12 weeks afterward.

Objective response rate served as the primary endpoint, with safety, duration of response, PFS and OS as secondary endpoints.

Median follow-up was 10.2 months (range, 0.6-22.7).

By the date of data cutoff, 88 patients had discontinued pembrolizumab, most (n = 64) because of disease progression. Median duration of pembrolizumab treatment was 2.9 months (range, 1 day-22.1 months). Median number of doses was five (range, 1-33).

Results showed an ORR of 12.2% (95% CI, 6.5-20.4), with three patients achieving a complete response and nine achieving a partial response.

The 12 responders all had PD-L1-positive tumors. The ORR among patients with PD-L1-positive tumors was 14.6% (95% CI, 7.8-24.2). The ORR among patients previously treated with chemotherapy for recurrent or metastatic disease was 14.3% (95% CI, 7.4-24.1).

Nine of the 12 patients who achieved a response continued to respond after 9 months or more. Median time to response was 2.1 months (range, 1.6-4.1) and median duration of response was not reached.

Eighty-four patients (85.7%) experienced disease progression or died (n = 68) by the time of data cutoff. Median PFS was 2.1 months (95% CI, 2-2.2), with an estimated 6-month PFS rate of 25%.

Median OS was 11 months (95% CI, 9.1-14.1) in the PD-L1-positive population and 9.4 months (95% CI, 7.7-13.1) in the total population.

Nearly two-thirds of patients (65.3%) experienced treatment-related adverse events, including hypothyroidism (10.2%), decreased appetite (9.2%), fatigue (9.2%) and diarrhea (8.2%). Grade 3 to grade 4 events, experienced by 12.2% of patients, included increased alanine aminotransferase (3.1%) and increased aspartate aminotransferase (2%). No treatment-related adverse events led to death.

“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” Chung and colleagues wrote. “Pembrolizumab is currently being tested in combination with concurrent chemoradiotherapy and with concurrent vs. sequential chemoradiotherapy for patients with locally advanced cervical cancer and with chemotherapy and bevacizumab [Avastin, Genentech] for patients with recurrent, persistent or metastatic cervical cancer.” – by John DeRosier

Disclosures: Chung reports honoraria from Eli Lilly, Foundation Medicine and Merck; consultant/advisory roles with Bristol-Myers Squibb, Celltrion, Eli Lilly, Merck Serono, Quintiles and Taiho Pharmaceutical; speakers bureau roles with Eli Lilly, Foundation Medicine and Merck Serono; and research funding from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Merck Serono and Taiho Pharmaceutical. Please see the study for all other authors’ relevant financial disclosures.

Pembrolizumab monotherapy appeared safe and induced durable antitumor responses in patients with advanced cervical cancer, according to interim results of the phase 2 KEYNOTE-158 study published in Journal of Clinical Oncology.

Based on these results, the FDA granted accelerated approval of pembrolizumab (Keytruda, Merck) for patients with advanced PD-L1-positive cervical cancer whose disease progressed during or after chemotherapy.

“Cervical cancer is the fourth leading cause of cancer-related mortality in women worldwide,” Hyun Cheol Chung, MD, PhD, professor at Yonsei University College of Medicine in Seoul, South Korea, and colleagues wrote. “In recent years, there has been a reduced incidence of cervical cancer in developed countries related to systematic screening, and we may expect the incidence and mortality rates to decline further if widespread vaccination against human papillomavirus is adopted.”

Chung and colleagues analyzed the safety and efficacy of pembrolizumab in a cohort of 98 patients (median age, 46 years; range, 24-75) with previously treated advanced cervical cancer. The cohort included 82 patients (83.7%) with PD-L1-positive tumors, 77 of whom had been treated for recurrent or metastatic cancer with one or more lines of chemotherapy.

Patients received 200 mg pembrolizumab every 3 weeks for 2 years or until disease progression, intolerable toxicity, or physician or patient decision to withdraw. Imaging of the tumor occurred every 9 weeks for the first year and every 12 weeks afterward.

Objective response rate served as the primary endpoint, with safety, duration of response, PFS and OS as secondary endpoints.

Median follow-up was 10.2 months (range, 0.6-22.7).

By the date of data cutoff, 88 patients had discontinued pembrolizumab, most (n = 64) because of disease progression. Median duration of pembrolizumab treatment was 2.9 months (range, 1 day-22.1 months). Median number of doses was five (range, 1-33).

Results showed an ORR of 12.2% (95% CI, 6.5-20.4), with three patients achieving a complete response and nine achieving a partial response.

The 12 responders all had PD-L1-positive tumors. The ORR among patients with PD-L1-positive tumors was 14.6% (95% CI, 7.8-24.2). The ORR among patients previously treated with chemotherapy for recurrent or metastatic disease was 14.3% (95% CI, 7.4-24.1).

Nine of the 12 patients who achieved a response continued to respond after 9 months or more. Median time to response was 2.1 months (range, 1.6-4.1) and median duration of response was not reached.

Eighty-four patients (85.7%) experienced disease progression or died (n = 68) by the time of data cutoff. Median PFS was 2.1 months (95% CI, 2-2.2), with an estimated 6-month PFS rate of 25%.

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Median OS was 11 months (95% CI, 9.1-14.1) in the PD-L1-positive population and 9.4 months (95% CI, 7.7-13.1) in the total population.

Nearly two-thirds of patients (65.3%) experienced treatment-related adverse events, including hypothyroidism (10.2%), decreased appetite (9.2%), fatigue (9.2%) and diarrhea (8.2%). Grade 3 to grade 4 events, experienced by 12.2% of patients, included increased alanine aminotransferase (3.1%) and increased aspartate aminotransferase (2%). No treatment-related adverse events led to death.

“These results show that treatment with pembrolizumab offers a clinically meaningful therapeutic option for a subset of patients with previously treated advanced cervical cancer,” Chung and colleagues wrote. “Pembrolizumab is currently being tested in combination with concurrent chemoradiotherapy and with concurrent vs. sequential chemoradiotherapy for patients with locally advanced cervical cancer and with chemotherapy and bevacizumab [Avastin, Genentech] for patients with recurrent, persistent or metastatic cervical cancer.” – by John DeRosier

Disclosures: Chung reports honoraria from Eli Lilly, Foundation Medicine and Merck; consultant/advisory roles with Bristol-Myers Squibb, Celltrion, Eli Lilly, Merck Serono, Quintiles and Taiho Pharmaceutical; speakers bureau roles with Eli Lilly, Foundation Medicine and Merck Serono; and research funding from Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Merck Sharp & Dohme, Merck Serono and Taiho Pharmaceutical. Please see the study for all other authors’ relevant financial disclosures.

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