KEYTRUDA - CBNPC 2eme ligne (pembrolizumab)

Key points

Favourable opinion for maintenance of reimbursement only in the treatment of locally advanced or metastatic non-small cell lung carcinoma (NSCLC) in adults whose tumours express PD-L1 with a ≥ 1% TPS and who have received at least one prior chemotherapy regimen. Patients with EGFR-positive (EGFR+) tumour mutations should also have received targeted therapy before receiving KEYTRUDA (pembrolizumab).

Unfavourable opinion for reimbursement in patients with ALK-positive (ALK+) tumour mutations, who should also have received targeted therapy before receiving KEYTRUDA (pembrolizumab).

What therapeutic improvement?

Therapeutic improvement compared to docetaxel in patients whose tumours express PD-L1 with a ≥ 1% TPS

In ALK + patients: not applicable.

Role in the care pathway?

Before the advent of PD-1 inhibitors, the care pathway for the treatment of non-small cell lung cancer (NSCLC) after failure of chemotherapy was as follows: in the absence of an activating EGFR mutation and ALK gene rearrangement, in eligible patients, it was recommended to propose second-line monotherapy, the nature of which depended on the drugs used previously: docetaxel or pemetrexed (only for non-squamous lung cancers).

Today, the second-line treatment of metastatic NSCLC is based on the administration of a PD-1 inhibitor if pembrolizumab has not been used as monotherapy or in combination (platinum and pemetrexed for non-squamous NSCLC; carboplatin and paclitaxel for squamous NSCLC) as metastatic first-line treatment in the event of PD-L1 ≥ 50%:

• OPDIVO (nivolumab) or,
• TECENTRIQ (atezolizumab) or,
• KEYTRUDA (pembrolizumab) only in the event of tumours with PD-L1 over-expression ≥ 1%.

Chemotherapy retains a second-line role in patients in whom first-line immunotherapy has failed.

In the event of activating EGF (EGFR) mutation, present in approximately 10% of cases of NSCLC, after the failure of tyrosine kinase inhibitor (TKI) monotherapy targeting the EGFR or the erlotinib – ramucirumab combination (CYRAMZA), it is recommended to test for the presence of a T790M+ mutation. Osimertinib (TAGRISSO) is the reference treatment in the event of a positive result for the mutation and if it has not been used as first-line therapy. If the result for the mutation is negative, the recommended treatment is platinum salt-based chemotherapy combined with one of the following drugs: gemcitabine, vinorelbine, taxanes (docetaxel and paclitaxel) or pemetrexed. Bevacizumab may be added depending on the case to some of these combinations for non-squamous NSCLC.

In patients with ALK+ NSCLC (3.5%), the therapeutic arsenal has been expanded with the addition of specific treatments targeting this genome abnormality: crizotinib (XALKORI), ceritinib (ZYKADIA), alectinib (ALECENSA).

Role of the medicinal product in the care pathway

After the failure of prior platinum-based chemotherapy, KEYTRUDA (pembrolizumab) as monotherapy is a second or later-line alternative, only in the event of tumours with PD-L1 over-expression ≥ 1%, to OPDIVO (nivolumab) or TECENTRIQ (atezolizumab) in patients with squamous or non-squamous, locally advanced or metastatic NSCLC.

In the absence of any comparative data, the role of KEYTRUDA (pembrolizumab) versus TECENTRIQ (atezolizumab) or OPDIVO (nivolumab) is not known.

In patients with an EGFR mutation, the role of KEYTRUDA (pembrolizumab) remain to be studied, with an optimal level of evidence.

In patients with an ALK gene rearrangement (ALK+), KEYTRUDA (pembrolizumab) has no role in the care pathway in the absence of clinical data.