EntrectinibRozlytrek
Treatment of locally advanced (Stage IIIB) or metastatic (Stage IV) c-ros proto-oncogene 1 (ROS1)-positive non-squamous or not otherwise specified (NOS) non-small cell lung cancer (NSCLC).
Decision on record
- Meeting Mar 2020 Recommended Non-small cell lung cancer (NSCLC)
Access path
- TGA registered · Rozlytrek
TGA label narrower than the PBS population
- Mar 2020Recommended · restricted
vs crizotinib
- PBS listing · Authority Required
From the public summary
The PBAC recommended the Authority Required listing of entrectinib as monotherapy for the treatment of patients with locally advanced (Stage IIIB) or metastatic (Stage IV) c-ros proto-oncogene 1 (ROS1)-positive non-squamous or not otherwise specified (NOS) non-small cell lung cancer (NSCLC).PSD · Mar 2020
The PBAC considered it would be appropriate to restrict entrectinib to ROS1 inhibitor naïve patients and patients who have developed intolerance to a ROS1-inhibitor given the evidence indicating a lack of response in patients who received previous treatment with a ROS1 inhibitor (see paragraph 3.3).PSD · Mar 2020
The submission presented a cost-minimisation analysis of entrectinib compared to crizotinib.PSD · Mar 2020
The submission assumed the duration of entrectinib treatment was the same as that of crizotinib and the equi-effective doses were estimated as entrectinib 600mg daily and crizotinib 250mg twice daily. The assumption of the same duration of treatment was based on the claim of non-inferiority in terms of PFS between entrectinib and crizotinib. 17PSD · Mar 2020
The submission described entrectinib as non-inferior in terms of both effectiveness and safety to crizotinib. The evaluation considered the claim was not adequately supported by the evidence presented in the submission, given the naïve indirect nature of the comparison provided, the considerable heterogeneity in the baseline characteristics between study populations, and differences in the duration of treatment and follow-up across the studies.PSD · Mar 2020
The results for the main patient-relevant outcome, overall survival, were immature in a number of studies, including the entrectinib ROS1-positive NSCLC PAS from the pooled entrectinib studies.PSD · Mar 2020
The PBAC noted and welcomed the input from individuals (6) and organisations (4) via the Consumer Comments facility on the PBS website. The comments were supportive of a listing for entrectinib on the PBS and emphasised the need for alternative treatment options for patients with ROS1-positive NSCLC, particularly where patients are unsuitable or intolerant to current treatment.PSD · Mar 2020
The PBAC noted the correspondence received from Peter MacCallum Cancer Centre, Rare Cancers Australia and Lung Foundation Australia were supportive for entrectinib to be included on the PBS for patients with ROS1-positive NSCLC. The correspondence indicated that a treatment that can penetrate the CNS would be beneficial in this patient population noting that metastases often occur in the brain.PSD · Mar 2020
Cost-effectiveness
Cost-minimisation analysis conducted; no ICER calculated by design.
The submission presented a cost-minimisation analysis of entrectinib compared to crizotinib. PSD · 2020
Decision context
PopulationPatients with ROS1-positive, locally advanced (Stage IIIB) or metastatic (Stage IV) non-squamous or NOS NSCLC, with WHO performance status of 2 or less, who have not received prior ROS1 receptor tyrosine kinase inhibitor treatment or who have developed intolerance to such treatment.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2020 | Recommended · restricted | crizotinib | — | Single-arm · ORR |
Clinical evidence
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| ROS1 FISH testing for NSCLC | ROS1 gene rearrangement | supported | 2020 |
| Small gene panel testing for NSCLC | EGFR, ALK, ROS1, MET exon 14, BRAF, KRAS, RET, NTRK1, NTRK2, NTRK3 | supported | 2022 |
Consumer voice
Six individuals and four organisations provided supportive comments for entrectinib listing on the PBS for ROS1-positive NSCLC patients. Comments emphasised the need for alternative treatment options and highlighted benefits including prolonged survival, improved quality of life, reduced hospital visits, and CNS penetration.
The comments were supportive of a listing for entrectinib on the PBS and emphasised the need for alternative treatment options for patients with ROS1-positive NSCLC, particularly where patients are unsuitable or intolerant to current treatment. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to non-squamous/NOS histology, PS ≤2, treatment-naive or intolerant, and first-line use; TGA label has no histology or performance status limits.