Historically, the standard of care for patients with locally advanced cervical cancer has been external beam radiotherapy with concurrent chemotherapy, followed by brachytherapy. Preclinical and clinical data has already established that the efficacy of chemoradiotherapy could be enhanced through the incorporation of immunotherapy.

ENGOT-cx11/GOG-3047/KEYNOTE-A18 is a Phase III randomized, triple-masked, multicenter trial evaluating the efficacy and safety of pembrolizumab in combination with concurrent chemoradiotherapy in 1,060 treatment-naive patients with high-risk locally advanced cervical cancer. Patients were randomized to receive concurrent chemoradiotherapy followed by brachytherapy, in combination with 200 mg pembrolizumab every three weeks for five cycles, followed by 500 mg pembrolizumab every six weeks for 15 cycles; or the same chemoradiotherapy regimen, in combination and maintenance with placebo.

In the initial analysis, with a median follow-up of 17.9 months (ranging from 0.9 to 31.0 months), the combination of pembrolizumab  and concurrent chemoradiotherapy demonstrated a statistically significant improvement in Progression-Free Survival (PFS) compared to a placebo in combination with concurrent chemoradiotherapy. The 24-month PFS rate was 67.8% for the pembrolizumab + concurrent chemoradiotherapy group, as opposed to 57.3% for the placebo + concurrent chemoradiotherapy group. The median PFS was not determined in either group, but the findings were consistent across all predefined subgroups. 

Although the data on Overall Survival (OS) is not yet mature, a favorable trend was reported for the pembrolizumab arm, with the pembrolizumab arm having a 24-month OS of 87.2%, while the placebo arm having a 24 month OS of 80.8%.

The safety profile of pembrolizumabarm─chemoradiotherapy combo was even better than expected, as the pembrolizumab arm showed <5% more serious (Grade 3–4) adverse events than the placebo arm, and only one patient in the pembrolizumab arm discontinued treatment due to side effect, which was not treatment related.

KOL insights

“The addition of pembrolizumab to the current standard of care is set to revolutionize the clinical practice for high-risk locally advanced cervical cancer, especially since a 30% reduction in the risk of progression in a setting where the treatment is potentially curative is of utmost importance” -Clinical Oncologist, Medical Gynecological Oncology Group, San Raffaele Scientific Institute Hospital, Italy

Conclusion

Pembrolizumab plus concurrent chemoradiotherapy showed a significant clinical improvement in PFS accompanied by a favorable trend in OS compared to placebo plus concurrent chemoradiotherapy, in treatment-naive patients with high-risk locally advanced cervical cancer and also demonstrated a manageable safety profile. These findings suggest that pembrolizumab in combination with concurrent chemoradiotherapy could potentially transform the standard of care for this population.

Cervical cancer is the fourth most frequently diagnosed cancer and the fourth leading cause of cancer death in women worldwide. DelveInsight estimates that the total incident population of Cervical Cancer in the 7MM will reach over 45,000 by 2032. Estimates show that the highest incident population of Cervical Cancer is in the United States followed by Japan and Germany.

For more insight into the patient's burden/epidemiology, treatment, and changing market landscape-related advancements, refer to the Cervical Cancer Market Insight and Forecast Report