ROZLYTREK (entrectinib) (CPNPC)

Key points

Unfavourable opinion for reimbursement in the treatment of adult patients with ROS1-positive (ROS1+), advanced non-small cell lung cancer (NSCLC) not previously treated with ROS1 inhibitors.

Role in the care pathway?

Currently, crizotinib is the only treatment to have a specific MA in ROS1-positive NSCLC. In its opinion of 13 May 2020, the Transparency Committee estimated that crizotinib had no role in the first-line treatment of ROS1+, advanced NSCLC. Before the arrival of crizotinib, the treatment of ROS1+, advanced NSCLC was based on chemotherapy combining a platinum-based drug with one of the following: taxane, pemetrexed (in non-squamous NSCLC), gemcitabine or vinorelbine. Bevacizumab can also be combined with this chemotherapy, in non-squamous NSCLC, in patients with an ECOG score of 0-1.

As second or later-line therapy, the use of crizotinib, or platinum-based chemotherapy is recommended.

Role of the medicinal product in the care pathway

 Considering:

• the very preliminary nature of the available efficacy data, based primarily on the results of a phase 2 non-comparative basket study (STARTRK-2) not meeting the Committee’s minimum requirements to provide formal evidence of the clinical benefit of ROZLYTREK (entrectinib),
• the absence of robust comparative data enabling assessment of the contribution of ROZLYTREK (entrectinib) in ROS1+ NSCLC compared to the available alternatives (chemotherapy or crizotinib), even though, notably, a direct comparative study would have been possible,
• the toxicity marked by an incidence of serious adverse events (AEs) reported in almost a third of patients (34%) and of grade ≥3 adverse events in more than one in two patients (56%),

the Transparency Committee considers that, on the basis of currently available data, ROZLYTREK (entrectinib) has no role in the care pathway.

It considers that in a context in which no robust comparative data is available to guarantee the solidity of the conclusion with respect to the effect of treatment with ROZLYTREK (entrectinib), the introduction of this medicinal product into the care pathway is accompanied by a higher risk than for medicinal products for which the efficacy is based on a comparison conducted with control of the risk of wrongly concluding that the treatment is effective (two-tailed alpha risk conventionally accepted to be 5%).