What is the administration protocol for the carboplatin (Carbo) + paclitaxel (Pacli) + bevacizumab (Beva) + pembrolizumab (Pembro) combination in metastatic cervical cancer?

From the Guidelines

The carboplatin + paclitaxel + bevacizumab + pembrolizumab combination in metastatic cervical cancer is administered as a 21-day cycle, with paclitaxel 175 mg/m² IV, carboplatin AUC 5 IV, bevacizumab 15 mg/kg IV, and pembrolizumab 200 mg IV on day 1 of each cycle, as supported by the latest guidelines from the Society for Immunotherapy of Cancer 1. The administration protocol typically involves paclitaxel infusion over 3 hours, followed by carboplatin infusion over 30-60 minutes, bevacizumab infusion over 30-90 minutes, and pembrolizumab infusion over 30 minutes. Key considerations for this regimen include:

• Premedication with dexamethasone, diphenhydramine, and H2 antagonists to prevent hypersensitivity reactions to paclitaxel
• Adequate hydration and antiemetics before carboplatin administration
• Regular monitoring for immune-related adverse events from pembrolizumab and hypertension, proteinuria, and bleeding risks from bevacizumab, as highlighted in the KEYNOTE-826 study 1 This combination therapy aims to improve response rates and survival outcomes in patients with metastatic cervical cancer by leveraging the cytotoxic effects of chemotherapy, the anti-angiogenic properties of bevacizumab, and the immune checkpoint inhibition of pembrolizumab, as recommended by the Society for Immunotherapy of 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.

The administration protocol for the carboplatin (Carbo) + paclitaxel (Pacli) + bevacizumab (Beva) + pembrolizumab (Pembro) combination in metastatic cervical cancer is:

• Pembrolizumab (Pembro): 200 mg every 3 weeks
• Chemotherapy: paclitaxel and carboplatin
• Bevacizumab (Beva): with or without bevacizumab 2

From the Research

Administration Protocol for Carbo + Pacli + Beva + Pembro Combination

The administration protocol for the carboplatin (Carbo) + paclitaxel (Pacli) + bevacizumab (Beva) + pembrolizumab (Pembro) combination in metastatic cervical cancer is not directly stated in the provided studies. However, we can look at the protocols used in similar combinations:

• In the study 3, paclitaxel 175 mg/m2, carboplatin area under the curve 6 mg/mL/min, and bevacizumab 15 mg/kg were administered every 21 days until disease progression, complete remission, or limiting toxicity.
• In the study 4, paclitaxel (175 mg/m2), carboplatin (AUC 5), and bevacizumab (15 mg/m2) were administered every three weeks until disease progression or unacceptable adverse events occurred.
• The study 5 used a combination of cisplatin 50 mg/m2 or carboplatin area under the curve of 5, paclitaxel 175 mg/m2, and bevacizumab 15 mg/kg, all on day 1 of every 3-week cycle, with or without atezolizumab 1200 mg.

Key Points to Consider

• The dosages and administration schedules may vary depending on the specific study or clinical trial.
• The combination of Carbo + Pacli + Beva + Pembro is not explicitly mentioned in the provided studies, but similar combinations have been used in clinical trials.
• The addition of an immune checkpoint inhibitor, such as pembrolizumab, to the standard backbone of chemotherapy and bevacizumab may improve progression-free and overall survival in metastatic cervical cancer, as seen in the study 5 with atezolizumab.

Similar Combinations and Their Efficacy

• The combination of paclitaxel, carboplatin, and bevacizumab has been shown to be effective and safe in patients with advanced or recurrent cervical cancer, with an objective response rate of 88% and a median progression-free survival of 10.8 months 3.
• The study 4 also demonstrated the efficacy and safety of paclitaxel-carboplatin and bevacizumab combination with maintenance bevacizumab therapy, with a median progression-free survival of 11.3 months and an overall response rate of 79.7%.