XALKORI

Reevaluation.

Favourable opinion for reimbursement only for the second and later-line treatment of adults with ROS1-positive advanced non-small cell lung cancer (NSCLC). In this indication, the clinical benefit is now low (previously it was moderate).

Now unfavourable opinion for reimbursement for the first-line treatment of adults with ROS1-positive advanced non-small cell lung cancer (NSCLC).

What therapeutic improvement?

No clinical added value in the therapeutic strategy.

Role in the care pathway?

Surgical treatment is recommended at the early stage of the disease, whereas systemic therapy is necessary at locally advanced or metastatic stages. This treatment is guided by the presence or otherwise of molecular abnormalities, the PD-L1 expression status of the tumour and the patient’s ECOG status.

ROS1 rearrangements, found in 1 to 2% of NSCLC cases, are exclusive of the other oncogenic mutations found in NSCLC (EGFR mutations, KRAS mutations, ALK fusions, etc.) and were discovered recently.

Crizotinib (XALKORI) is the first treatment to have an MA in ROS1-positive NSCLC. Before the arrival of crizotinib, the treatment of ROS1-positive NSCLC was based on platinum-based chemotherapy. Some recommendations also propose the off-label use of ceritinib (ZYKADIA).

As second or later-line therapy, the use of crizotinib (XALKORI), if it was not used as first-line therapy, or chemotherapy (platinum or pemetrexed-based) is recommended. Only the American guidelines recommend the use of immunotherapy (pembrolizumab or atezolizumab) in combination with chemotherapy, in the event of positive PDL-1 expression (≥ 1%), and the absence of contraindications and for patients in good general condition (ECOG 0-1).

Role of the medicinal product in the care pathway:

Considering:

• the absence of solid data concerning the prognostic value of positive ROS1 expression,
• the absence of robust comparative data for XALKORI (crizotinib) versus the chemotherapy conventionally used in ROS1-positive NSCLC patients, despite the Committee’s initial request, in a context in which the comparative data from the ESME observational study are exploratory, making it possible to assess the additional contribution of XALKORI (crizotinib) in the therapeutic strategy,
• uncertainties concerning the transposability of the results to clinical practice in patients receiving first-line therapy, given their low proportion in the studies (15% of study population),
• and its preferential use as second and later-line therapy in clinical practice in accordance with the data provided in real-life conditions,

the Committee considers that the role of XALKORI (crizotinib) is as second and later-line therapy only in previously-treated ROS1-positive NSCLC patients. XALKORI (crizotinib) no longer has a role to play in first-line therapy in chemotherapy-naive patients.