Can cervical cancer be treated with a combination of pembrolizumab (Pembrolizumab) and bevacizumab (Bevacizumab) and chemotherapy, such as carboplatin and paclitaxel, in the second-line setting?

From the Guidelines

Yes, cervical cancer can be treated with a combination of pembrolizumab, bevacizumab, and chemotherapy (carboplatin and paclitaxel) in the second-line setting, as this approach has shown improved progression-free survival (PFS) and overall survival (OS) in patients with persistent, recurrent, or metastatic PD-L1-positive cervical cancer 1. This treatment strategy combines immunotherapy (pembrolizumab), anti-angiogenic therapy (bevacizumab), and cytotoxic chemotherapy to target the cancer through multiple mechanisms.

• Typically, pembrolizumab is administered at 200 mg intravenously every 3 weeks,
• bevacizumab at 15 mg/kg every 3 weeks,
• carboplatin at AUC 5, and
• paclitaxel at 175 mg/m² every 3 weeks. Treatment usually continues until disease progression or unacceptable toxicity occurs. This combination has shown promise in clinical practice by enhancing immune response against cancer cells, inhibiting tumor blood vessel formation, and directly killing cancer cells. Patients should be monitored for immune-related adverse events from pembrolizumab, bleeding or hypertension from bevacizumab, and myelosuppression from chemotherapy. Regular assessments of treatment response through imaging and clinical evaluation are essential. This approach may be particularly beneficial for patients who have progressed after first-line platinum-based therapy, as evidenced by the KEYNOTE-826 study, which demonstrated superiority of pembrolizumab combination therapy in terms of PFS and OS in the PD-L1 CPS≥1 population 1. Although other studies have explored different combinations, such as paclitaxel, ifosfamide, and cisplatin (TIP), or bevacizumab with chemotherapy, the most recent and highest quality evidence supports the use of pembrolizumab, bevacizumab, and chemotherapy in the second-line setting for cervical cancer 1.

From the FDA Drug Label

The safety of KEYTRUDA in combination with paclitaxel and cisplatin or paclitaxel and carboplatin, with or without bevacizumab, was investigated in KEYNOTE-826, a multicenter, double-blind, randomized (1:1), placebo-controlled trial in patients with persistent, recurrent, or first-line metastatic cervical cancer who had not been treated with chemotherapy except when used concurrently as a radio-sensitizing agent A total of 616 patients, regardless of tumor PD-L1 expression, received KEYTRUDA 200 mg and chemotherapy with or without bevacizumab (n=307) every 3 weeks or placebo and chemotherapy with or without bevacizumab (n=309) every 3 weeks.

Cervical Cancer Treatment:

• Second-line treatment: The provided drug labels do not directly address the use of pembrolizumab, bevacizumab, and chemotherapy (such as carboplatin and paclitaxel) in the second-line setting for cervical cancer.
• KEYNOTE-826 trial: This trial investigated the safety of KEYTRUDA (pembrolizumab) in combination with chemotherapy (paclitaxel and cisplatin or paclitaxel and carboplatin) with or without bevacizumab in patients with persistent, recurrent, or first-line metastatic cervical cancer.
• KEYNOTE-158 trial: This trial investigated the efficacy of KEYTRUDA in patients with recurrent or metastatic cervical cancer, but it does not provide information on the use of pembrolizumab, bevacizumab, and chemotherapy in the second-line setting.

Based on the provided information, no conclusion can be drawn about the use of pembrolizumab, bevacizumab, and chemotherapy (such as carboplatin and paclitaxel) in the second-line setting for cervical cancer 2, 2.

From the Research

Treatment of Cervical Cancer with Pembrolizumab, Bevacizumab, and Chemotherapy

• The treatment of cervical cancer with a combination of pembrolizumab, bevacizumab, and chemotherapy, such as carboplatin and paclitaxel, in the second-line setting is a topic of interest in oncology.
• Studies have shown that the combination of paclitaxel, carboplatin, and bevacizumab is effective and safe in patients with advanced or recurrent cervical cancer 3, 4.
• The addition of bevacizumab to paclitaxel plus carboplatin has been shown to increase treatment response and overall survival in advanced cervical cancer women, but it may also increase adverse effects such as neutropenia, leukopenia, anemia, hypertension, and gastrointestinal fistula 4.
• Pembrolizumab, a checkpoint inhibitor, has been shown to increase median overall survival when used in the first line with platinum-paclitaxel-bevacizumab in advanced cervical cancer patients 5.
• However, there is limited information available on the use of pembrolizumab in the second-line setting for cervical cancer treatment.

Efficacy and Safety of Combination Therapies

• The combination of paclitaxel, carboplatin, and bevacizumab has been shown to have an objective response rate of 88% and a complete response rate of 50% in patients with advanced or recurrent cervical cancer 3.
• The safety profile of this combination has been evaluated, and common adverse effects include neutropenia, leukopenia, anemia, and thrombocytopenia 3, 4.
• The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer 6.

Future Directions

• There is still an unmet need for new, more effective treatments for advanced cervical cancer, and significant efforts are needed in the discovery of drugs beyond the current 'me-too' drugs 5.
• Further studies are needed to evaluate the efficacy and safety of combination therapies, including pembrolizumab, bevacizumab, and chemotherapy, in the second-line setting for cervical cancer treatment.