Rahim ağzı(serviks) kanserinde yeni tedavi seçeneği olarak kemoradiyoterapi ve pembrolizumab pemrolizumab tedavisi
Rahim ağzı(serviks) kanserinde yeni tedavi seçeneği olarak kemoradiyoterapi ve pembrolizumab pemrolizumab tedavisi
Serviks kanseri kadınlarda sık görülen bir kanser ve büyük oranda HPV virüsünün cinsel yola bulaşmasında oluşur.
Aşılama programları ile hastalık büyük oranda engellenebilir.
Cerrahi aşamasını geçmiş serviks kanserinde (Evre IB2-IVA) standart tedavi olan kemoradiyoterapi (sisplatin haftalık) tedavisine immünoterapi eklenmesi ile hastalığın nüks gelişiminde önemli oranda azalma saptandı.
Faz III ENGOT-cx11/GOG-3047/KEYNOTE-A18 çalışması uzun yıllar sonra ilk sefer standart tedaviye bir molekülün eklenmesi ile rahim ağzı kanserinin sonuçlarında olumlu bir gelişme olduğunu gösterdi.
Çalışma standart tedavi olan Radyoterapi ve haftalık sisplatin(40mg/m2) sonrası brakiterapi tedavisine, radyoterapi esnasında pembrolizumab 200 mg üç haftada bir 4 kez sonrası, 400 mg 15 kez şeklinde eklenmesi yapılmış.
Hastalığın progresyonunda(ilerlemesinde) immünoterapi eklenen kolda %11 oranında daha iyi ek sonuç elde edilmiş.
Bu fayda özelikle evre III ve IVA hasta grubunda daha belirgin olduğu saptanmıştır.
Yeni ilacın eklenmesi ile özelikle immünite ilişkili yan etkilerin olduğu ve bunun hiper ya da hipotiroidi fonksiyonları ile ilişkili olduğu saptandı.
Bu çalışma ile ameliyat olamayan lokal iler serviks kanserine kemoradioterapi tedavisine pemrolizumab eklenmesi yeni bir tedavi seçeneği olduğu gösterildi.
Kaynak
Chemoradiotherapy With or Without Pembrolizumab for Newly Diagnosed, High-Risk, Locally Advanced Cervical Cancer
As reported in The Lancet Oncology by Domenica Lorusso, MD, PhD, and colleagues, the phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 trial has shown that the addition of pembrolizumab to chemoradiotherapy improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer.
Data from the trial supported the January 2024 approval of pembrolizumab with chemoradiotherapy in patients with International Federation of Gynecology and Obstetrics (FIGO) 2014 stage III to IVA disease on the basis of significantly improved progression-free survival.
Study Details
The double-blind trial included 1,060 patients with FIGO stage IB2 to IIB node-positive to stage III to IVA disease from sites in 30 countries. They were randomly assigned between June 2020 and December 2022 to receive 5 cycles of pembrolizumab at 200 mg (n = 529) or placebo (n = 531) every 3 weeks plus chemoradiotherapy, followed by 15 cycles of pembrolizumab at 400 mg or placebo every 6 weeks. Chemoradiotherapy included five cycles of cisplatin at 40 mg/m2 once weekly plus external-beam radiotherapy followed by brachytherapy. A total of 598 patients (56.4%) had stage III to IVA disease. The primary endpoints of the study were investigator-assessed progression-free survival and overall survival in the intention-to-treat population.
Efficacy Outcomes
At data cutoff in January 2023, median follow-up was 17.9 months (interquartile range = 11.3–22.3 months) in both treatment groups. Median progression-free survival was not reached in either group. Estimated rates at 24 months were 68% (95% confidence interval [CI] = 62%–73%) in the pembrolizumab/chemoradiotherapy group vs 57% (95% CI = 51%–63%) in the placebo/chemoradiotherapy group (hazard ratio [HR] = 0.70, 95% CI = 0.55–0.89, P = .0020).
Among 294 vs 304 patients with stage III to IVA disease, the hazard ratio for the pembrolizumab/chemotherapy group vs the placebo/chemotherapy group for progression-free survival was 0.58 (95% CI = 0.42–0.80). Among 235 vs 227 patients with stage IB2 to IIB disease, the hazard ratio was 0.91 (95% CI = 0.63–1.31).
At time of analysis of overall survival (42.9% information fraction), estimated overall survival at 24 months among all patients was 87% (95% CI = 82%–91%) in the pembrolizumab/chemoradiotherapy group vs 81% (95% CI =75%–86%) in the placebo/chemoradiotherapy group (HR = 0.73, 95% CI = 0.49–1.07).
KEY POINTS
The addition of pembrolizumab to chemoradiotherapy improved progression-free survival.
Benefit was most marked among patients with stage III to IVA disease.
Adverse Events
Grade ≥ 3 treatment-related adverse events occurred in 67% of patients in the pembrolizumab/chemoradiotherapy group vs 61% of those in the placebo/chemoradiotherapy group. The most common in the pembrolizumab/chemoradiotherapy group were anemia (19% vs 16% in control group), decreased white blood cells (19% vs 21%), and decreased neutrophils (15% vs 15%). Serious treatment-related adverse events occurred in 17% vs 12% of patients. Treatment-related adverse events led to discontinuation of any treatment component in 15% vs 13% of patients. Any grade immune-related adverse events in the pembrolizumab/chemoradiotherapy group included hypothyroidism in 19% and hyperthyroidism in 11%. Treatment-related adverse events led to death in two patients in the pembrolizumab/chemoradiotherapy group (due to immune-mediated gastritis and large intestine perforation) and in two in the placebo/chemoradiotherapy group (due to bone marrow failure and neutropenic colitis).
The investigators concluded, “Pembrolizumab plus chemoradiotherapy significantly improved progression-free survival in patients with newly diagnosed, high-risk, locally advanced cervical cancer.”
