The addition of pembrolizumab to modern and high-quality chemoradiotherapy significantly improved overall survival (OS) in patients with locally advanced cervical cancer, according to results from the phase 3 KEYNOTE-A18 study.
In recent years, modern, high-quality radiotherapy has increased local control and OS, as well as reduced toxicity of the treatment of locally advanced cervical cancer1. In addition, pembrolizumab, alone or in combination with chemotherapy, has shown efficacy and manageable safety in patients with recurrent or metastatic cervical cancer2.
The multicenter, phase 3 KEYNOTE-A18 trial (NCT04221945) evaluated the efficacy and safety of combined pembrolizumab, radiotherapy, and concurrent chemotherapy in patients with locally advanced cervical cancer. Enrolled were 1,060 participants with newly diagnosed, high-risk, locally advanced cervical cancer (FIGO stage IB2-IIB [node positive] or stage III–IVA), were randomly assigned five cycles of pembrolizumab or placebo plus chemoradiotherapy, followed by 15 cycles of pembrolizumab or placebo. Recently, the first results from KEYNOTE-A18 were published, showing a statistically significant progression-free survival (PFS) benefit of pembrolizumab/chemoradiotherapy over chemoradiotherapy alone (HR 0.70; 95% CI 0.55–0.89; P=0.002)3. Domenica Lorusso, MD, PHD, from Humanitas San Pio X, in Italy now presented OS results, a primary endpoint of KEYNOTE-A184.
After a median follow-up of 29.9 months, the median OS was not reached in both arms. Adding pembrolizumab significantly increased the estimated 3-year OS rate: 82.6% versus 74.8% (HR 0.67; 95% CI 0.50–0.90; P=0.0040). Pembrolizumab/chemoradiotherapy also favored overall response rate (87.5% vs 83.7%), complete response rate (63.0% vs 56.5%), and duration of response (77.2% vs 67.0% at 2 years).
As expected, more immune-related AEs were reported in the pembrolizumab arm (39.0% vs 17.0%), however, most were of grade 1. The rate of treatment discontinuation was 20.6% in the pembrolizumab arm, versus 14.9% in the chemoradiotherapy alone arm.
“These data support pembrolizumab plus concordant chemoradiotherapy as the new standard-of-care for patients with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer,” concluded Prof. Lorusso.
Medical writing support was provided by Marten Dooper.
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