RETSEVMO (selpercatinib) - Non-small cell lung cancer (NSCLC)

New indication.

Key points

Unfavourable opinion for reimbursement, in first-line therapy, as monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC).

Maintenance of the favourable opinion for reimbursement, in second and later-line therapy only, as monotherapy for the treatment of adult patients with rearranged during transfection (RET) fusion-positive advanced non-small cell lung cancer (NSCLC). (See Transparency Committee opinion of 2 June 2021). This opinion of June 2021 had been conditional on the reassessment of this medicinal product within a maximum period of three years on the basis of the results of the phase 3 study in first-line treatment (LIBRETTO-431, primary analysis for end 2023) in RET fusion-positive NSCLC, in this indication.

What therapeutic improvement?

No clinical added value, on the basis of currently available data.

Role in the care pathway?

At the advanced stage of non-small cell lung cancer (NSCLC), patients are not eligible for surgery and their treatment is based on systemic therapy.

The first-line treatment of advanced NSCLC, in the absence of molecular abnormalities (EGFR mutations, or ALK or ROS-1 rearrangements) or in the presence of a molecular alteration for which no targeted therapy is currently available), is based on immunotherapy or immuno-chemotherapy, for eligible patients.

The second-line treatment of NSCLC is based on: 

• the administration of a PD-1/ PD-L1 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), TECENTRIQ (atezolizumab) or KEYTRUDA
  (pembrolizumab) only in the event of tumours with PD-L1 over-expression ≥ 1%;
• chemotherapy with, in particular, pemetrexed-based protocols if this has not previously been used, or docetaxel-based protocols.

In France, the AURA 2022 guidelines recommend RET inhibitors (selpercatinib or pralsetinib) as second-line therapy following platinum-based chemotherapy in patients with RET-positive advanced NSCLC, with optional referral to a clinical trial to enable them to benefit from a specific treatment targeting RET alterations. These two medicinal products, selpercatinib (RETSVEMO) and pralsetinib (GAVRETO), received a favourable opinion for reimbursement in 2021 (low clinical benefit and CAV V) as second-line therapy in patients with RET-positive advanced NSCLC.

In its 2022 American guidelines, the NCCN recommends the preferential use of selpercatinib or pralsetinib as first-line treatment when RET fusion has been detected before the initiation of treatment and following progression with first-line systemic treatment.

Role of the medicinal product in the care pathway:

Considering:

• the lack of robustness of the data available in a small number of patients included in the phase 1/2 multi-cohort study and from a subgroup of patients naive to prior systemic treatment (n = 69);
• the impossibility of assessing the contribution of RETSEVMO (selpercatinib) compared to chemotherapies in the absence of a direct comparison (single-arm trial) despite this comparison being possible;
• the existence of a phase 3 study, in first-line therapy, assessing RETSEVMO (selpercatinib) compared to pemetrexed combined with platinum-based chemotherapy and combined or otherwise with pembrolizumab, for which the results of the final analysis are expected by the end of 2023;

The Committee considers that, on the basis of currently available data, RETSEVMO (selpercatinib) has no role in the care pathway as first-line treatment in previously untreated patients.

In second and later-line treatment, the Committee considers that the role in the care pathway of RETSEVMO (selpercatinib) remains unchanged relative to the assessment conducted on 2 June 2021.