The United Kingdom’s National Institute for Health and Care Excellence has issued draft guidance recommending the approval of pembrolizumab plus chemotherapy for the treatment of patients with PD-L1–positive metastatic triple-negative breast cancer.
The United Kingdom’s National Institute for Health and Care Excellence (NICE) has issued draft guidance recommending the approval of pembrolizumab (Keytruda) plus chemotherapy for the treatment of patients with PD-L1–positive metastatic triple-negative breast cancer (TNBC) who have not received chemotherapy in the metastatic setting and who are not eligible for surgery.1
The recommendation is for patients with TNBC with a PD-L1 at combined positive score (CPS) of 10 or above and an immune cell staining (IC) less than 1%. The drug is to be used in combination with paclitaxel or nab-paclitaxel (Abraxane).
The agency is expected to publish its final recommendation by June 29, 2022.
NICE already recommends atezolizumab (Tecentriq) plus chemotherapy for untreated PD-L1–positive, locally advanced or metastatic TNBC with IC of at least 1%.
“People who were not able to access atezolizumab, another NICE-recommended immunotherapy, now have an important new option that can help them live longer and spend more precious time with their loved ones,” Helen Knight, program director in the NICE Centre for Health Technology Evaluation, stated in a press release. “Although our recommendation is for a narrower population than pembrolizumab combination is licensed for, it means the maximum number of people with advanced TNBC now have access to effective treatments.”
As is standard with NICE recommendations, Merck agreed to a commercial arrangement that makes pembrolizumab available to the National Health Service (NHS) at a discount. The amount of the discount was not disclosed.
In March 2022, NICE concluded that the long-term benefit of pembrolizumab plus chemotherapy was unclear in patients with metastatic, PD-L1–positive TNBC, even though the regimen was more effective than paclitaxel.2 At the time, NICE regulators reasoned Merck did not provide data showing a direct comparison between pembrolizumab plus chemotherapy vs atezolizumab plus chemotherapy. The agency also determined that cost-effectiveness estimates for pembrolizumab in combination with chemotherapy are higher than what it considers to be an acceptable use of NHS resources.
In its resubmission, Merck successfully argued that the pembrolizumab regimen should be compared with paclitaxel and docetaxel. Investigators estimated a 5-year survival rate of 20% and a 10-year survival rate of 10% for those receiving pembrolizumab compared with 10% and 0%, respectively, for those receiving paclitaxel or docetaxel.3
NICE based its decision on data from the 2-part, phase 3 KEYNOTE-355 trial (NCT02819518), which evaluated pembrolizumab in combination with investigator's choice of either nab-paclitaxel, paclitaxel, or gemcitabine/carboplatin, vs placebo plus 1 of the 3 chemotherapy agents in patients with previously untreated locally recurrent inoperable or metastatic TNBC (N = 847).
In final results presented at the 2021 ESMO Congress, among patients with a PD-L1 CPS of at least 10, the median overall survival was 23.0% in the experimental arm and 16.1% in the control arm (HR, 0.73; 95% CI, 0.55-0.95; P = .0093). The median progression-free survival was 9.7 vs 5.6 months, respectively (HR, 0.66; 95% CI, 0.50-0.88).4
On May 24, the European Commission approved pembrolizumab plus chemotherapy as neoadjuvant therapy, followed by adjuvant pembrolizumab monotherapy for adults with locally advanced or early-stage TNBC at high risk of recurrence.5 The approval was based on data from the pivotal phase 3 KEYNOTE-522 trial (NCT03036488).
In July 2021, the FDA approved the combination based on these same findings.6
KEYNOTE-522 compared pembrolizumab plus carboplatin and paclitaxel, followed by doxorubicin or epirubicin and cyclophosphamide prior to surgery and continued as monotherapy following surgery vs neoadjuvant chemotherapy alone in patients with untreated stage II or stage III TNBC. At a median follow-up of 39.1 months, the pembrolizumab combination induced a significant improvement in event-free survival (HR, 0.63; 95% CI, 0.48-0.82; P = .001).7