KEYTRUDA (pembrolizumab) - Cervical cancer

The Committee deems that the clinical benefit of KEYTRUDA (pembrolizumab), in combination with chemoradiotherapy (external beam radiation therapy followed by brachytherapy), is substantial in the indication: “in combination with chemoradiotherapy (external beam radiation therapy followed by brachytherapy), in the treatment of FIGO 2014 Stage III (extension onto the pelvic wall or lower one-third of the vagina and/or causing hydronephrosis or non-functioning kidney) to IVA (involvement of the mucosa of bladder/rectum -adjacent pelvic organ spread-) with or without involvement of the pelvic and/or para-aortic lymph nodes) locally advanced cervical cancer in adults who have not received prior definitive therapy.”

Considering:

• demonstration in a randomised, double-blind, phase 3 study (KN-A18 trial, including 56.7% FIGO 2014 stage III - IVA patients) of the superiority of pembrolizumab compared to chemoradiotherapy, for the treatment of FIGO stage IB2-IIB and III - IVA locally advanced cervical cancer in adults who have not received prior definitive therapy, in terms of:
  • progression-free survival with an HR = 0.70 (95% CI = [0.55; 0.89]; p = 0.002 < the predefined threshold of 0.0172), 7% patients progressed or died in the experimental group versus 29.0% patients in the control group. The median PFS was not reached in either of the two groups.
  • overall survival with an HR = 0.67 (95% CI = [0.50; 0.90]; p = 0.0040 < 0.01026), 2% deaths in the experimental group versus 20.5% patients in the control group. The median OS was not reached in either of the two groups.

And despite:

• the absence of any formal conclusion that can be drawn based on the quality of life findings;
• a safety profile deemed to be acceptable compared to chemoradiotherapy but marked by an excess toxicity with grade ≥ 3 AEs reported in 78.3% of patients in the pembrolizumab group and 70.0% of patients in the placebo group). In addition, 20.6% of patients in the pembrolizumab group and 14.9% of patients in the placebo group had an AE resulting in definitive discontinuation of pembrolizumab treatment.

The Committee deems that KEYTRUDA (pembrolizumab) 25 mg/ml, concentrate for solution for infusion, in combination with chemoradiotherapy (external beam radiation therapy followed by brachytherapy), provides a moderate clinical added value (CAV III) compared to chemoradiotherapy.