OBR OncologyFDA Approves Pembrolizumab Combination for Advanced Cervical Cancer

Enhanced Efficacy in Cervical Cancer Treatment: Pembrolizumab Plus CRT’s Role in Improving Patient Outcomes

The FDA’s recent approval of pembrolizumab in combination with chemoradiotherapy (CRT) marks a significant advancement in the treatment of FIGO 2014 stage III-IVA cervical cancer. This decision, rooted in the findings of the KEYNOTE-A18 clinical trial, showcases the improved progression-free survival rates among patients, highlighting the evolving landscape of cervical cancer management. This summary delves into the key aspects of the study, offering insights into the efficacy, safety, and clinical implications of this combined therapy.

Key Points:

1. FDA Approval: Pembrolizumab (Keytruda) plus CRT has been approved for treating FIGO 2014 stage III-IVA cervical cancer.
2. Clinical Trial Base: The approval was based on the KEYNOTE-A18 trial, a multicenter, randomized, double-blind, placebo-controlled phase 3 study.
3. Study Population: Enrolled 1,060 cervical cancer patients, with 596 having FIGO 2014 stage III–IVA and 462 having stage IB2–IIB, node-positive disease.
4. Treatment Regimen: Pembrolizumab at 200 mg or placebo every three weeks for five cycles with CRT, followed by pembrolizumab 400 mg or placebo every six weeks for 15 cycles.
5. CRT Details: CRT included weekly intravenous cisplatin (40 mg/m2 for up to six cycles) and external beam radiation therapy followed by brachytherapy.
6. Efficacy Outcomes: Main efficacy outcomes were progression-free survival (PFS) and overall survival (OS).
7. PFS Improvement: Pembrolizumab group showed significantly improved 24-month PFS (67.8%) compared to the placebo group (57.3%).
8. Subgroup Analysis: Significant benefit in PFS primarily in patients with later-stage disease (FIGO 2014 stage III–IVA).
9. Adverse Reactions: Fatal reactions in 1.4% of patients; most common serious adverse reactions were urinary tract infection, urosepsis, and sepsis.
10. Common Adverse Events: Included nausea, diarrhea, urinary tract infections, fatigue, and hypothyroidism, among others.
11. Dosage Recommendation: 200 mg every three weeks or 400 mg every six weeks, for up to 24 months or until disease progression/unacceptable toxicity.

Cervical cancer is the fourth most common cancer in women worldwide, with an estimated 604,000 new cases and 342,000 deaths in 2020.

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