Favourable opinion for reimbursement in the following indication: “KEYTRUDA, 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.”
Clinical Benefit
Substantial
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.”
Clinical Added Value
moderate
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.
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