KEYTRUDA

• Key points

Favourable opinion for reimbursement of KEYTRUDA (pembrolizumab) as monotherapy or in combination with platinum and 5‑fluorouracil (5‑FU) chemotherapy in the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma (HNSCC) in adults whose tumours express PD-L1 with a CPS ≥ 1.

• What therapeutic improvement?

KEYTRUDA (pembrolizumab) as monotherapy or in combination with platinum and 5-fluorouracil (5-FU) chemotherapy provides a therapeutic improvement compared to the EXTREME protocol in the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma in adults whose tumours express PD-L1 with a CPS ≥ 1.

• Role in the care pathway?

In patients receiving first-line treatment, in its opinion of 10 February 2010, the Transparency Committee recognised the EXTREME protocol as a standard therapy for patients with head and neck squamous cell carcinoma as first-line treatment, considering that the superiority of the proprietary medicinal product ERBITUX (cetuximab) in combination with platinum chemotherapy compared to in platinum-based chemotherapy alone was established in these situations (recurrent and/or metastatic) in terms of overall survival.

Role of KEYTRUDA (pembrolizumab) as monotherapy/combination with chemotherapy

KEYTRUDA (pembrolizumab) as monotherapy or in combination with chemotherapy is indicated for the first-line treatment of metastatic or unresectable recurrent head and neck squamous cell carcinoma[1] in adults whose tumours express PD-L1 with a CPS ≥ 1.

Its superiority as monotherapy or in combination with chemotherapy was demonstrated versus an acceptable comparator (EXTREME protocol) in terms of overall survival in patients in good general condition whose tumours express PD-L1 with a CPS ≥ 1, but with no impact on progression-free survival.

Given the design of the multi-arm KEYNOTE-048 study, which was not constructed to compare KEYTRUDA (pembrolizumab) as monotherapy versus KEYTRUDA (pembrolizumab) in combination with chemotherapy in patients with a CPS ≥ 1, this study does not enable the two treatment regimens to be ranked in this population.

Although the KEYNOTE-048 study tested the efficacy in the CPS ≥ 20 subpopulation, with results available in this subgroup - supplementing the results available in the CPS ≥ 1 population - the Committee considers that the threshold of 20 should not be used in clinical practice to determine the eligibility of the patient for treatment with KEYTRUDA (pembrolizumab) as monotherapy or in combination with chemotherapy, in accordance with its MA label. In fact, randomisation was conducted on the basis of a TPS level ≥ or < 50% and the contribution of KEYTRUDA cannot be formally quantified in the subgroup of patients with a CPS of between 1 and 20.  Furthermore, the EMA accepted an overall CPS ≥ 1 for the MA.

Consequently, the Committee proposes that the choice of treatment between KEYTRUDA (pembrolizumab) as monotherapy or in combination with chemotherapy in patients with a CPS ≥ 1 should be made taking into account:

- the patient’s general condition,

- the more favourable safety profile of monotherapy compared to the combination,

- the hyperprogressor status, with a life-threatening tumour mass, in particular located close to large vessels, which could guide the choice towards KEYTRUDA (pembrolizumab) in combination with chemotherapy versus monotherapy (expert opinion).

Finally, the Committee highlights that no data are available in nasopharyngeal carcinoma, which was an exclusion criterion in the KEYNOTE-048 study.

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