Increased OS with pembrolizumab in newly diagnosed, high-risk, locally advanced cervical cancer

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 cancer [1]. In addition, pembrolizumab, alone or in combination with chemotherapy, has shown efficacy and manageable safety in patients with recurrent or metastatic cervical cancer [2].

The multicentre, phase 3 KEYNOTE-A18 trial (NCT04221945) evaluated the efficacy and safety of combined pembrolizumab, external beam radiotherapy + brachytherapy, and concurrent chemotherapy in patients with locally advanced cervical cancer. Enrolled were 1,060 participants with newly diagnosed, high-risk, locally advanced cervical cancer (i.e. FIGO 2014 stage IB2-IIB [node positive] or stage III–IVA), who were randomised 1:1 to receive 5 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]. Prof. Domenica Lorusso (Humanitas Hospital San Pio X, Italy) now presented OS results, a primary endpoint of KEYNOTE-A18 [4].

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 favoured 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 adverse events 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 concomitant chemoradiotherapy followed by brachytherapy as the new standard-of-care for patients with newly diagnosed, previously untreated, high-risk, locally advanced cervical cancer,” concluded Prof. Lorusso

1. Potter R, et al. Lancet Oncol. 2021;22:538-547.
2. Monk B, et al. J Clin Oncol. 2023;41:5505-5511.
3. Lorusso D, et al. Lancet 2024;403:1341-1350.
4. Lorusso D, et al. Pembrolizumab plus chemoradiotherapy for high-risk locally advanced cervical cancer: Overall survival results from the randomized, double-blind, phase III ENGOT-cx11/GOG-3047/KEYNOTE-A18 study. Abstract 709O, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024