CrizotinibXalkori
Recommended OncologyAuthority Required 💬 consumer voice
Treatment of patients with locally advanced (Stage IIIB) or metastatic (Stage IV) ROS1-positive non-small cell lung cancer (NSCLC).
6
Submissions
4 resub
2013–18
On the record
$45k–200k
ICER range
4 sourced ICERs · 2014–2018
ICER stated
Cost basis
Decisions on record
- Meeting Jul 2018 Recommended Stage IIIB (locally advanced) or Stage IV (metastatic) non-small cell lung cancer (NSCLC) with a ROS1 gene rearrangement confirmed by fluorescent in situ hybridisation (FISH) testing
- Meeting Nov 2017 Deferred Stage IIIB (locally advanced) or Stage IV (metastatic) non-small cell lung cancer (NSCLC) with a ROS1 gene rearrangement confirmed by fluorescent in situ hybridisation (FISH) testing
- Meeting Mar 2017 Recommended Non-small cell lung cancer
- Meeting Nov 2014 Recommended capsules, 200 mg and 250 mg, Xalkori® Pfizer Australia Pty Ltd New listing (Minor submission) Non-small cell lung cancer To address key issues raised in the March 2014 PBAC deferral of crizotinib for the treatment of anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer. The initial e
- Meeting Mar 2014 Deferred Xalkori® Pfizer Australia Pty Ltd Non-small cell lung cancer (NSCLC) A resubmission to request Authority Required listing for treatment of a patient with Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC) who meets certain criteria. Sponsor Comment: Pfizer is committed to w
- Meeting Nov 2013 Deferred 200 mg and 250 mg, capsule Xalkori® Pfizer Australia Pty Ltd Major submission Non-small cell lung cancer (NSCLC) Authority Required listing for treatment of a patient with Anaplastic Lymphoma Kinase (ALK) positive non-small cell lung cancer (NSCLC) who has disease progression following at least one
Access path
- TGA registered · Xalkori
TGA label narrower than the PBS population
- Nov 2013Recommended · restricted
vs pemetrexed
- Mar 2014Deferred
- Nov 2014Recommended · restricted
ICER rose $75,000 → $200,000 (+167%)
- Mar 2017Recommended
ICER dropped $200,000 → $75,000 (-62%)
- Nov 2017Deferred
Comparator changed: chemotherapy (non-exchangeable trial comparison arms) → pemetrexed
- Jul 2018Recommended
- PBS listing · Authority Required
RecommendedDeferredNot recommended
From the public summary
PBAC outcome
6.1 The PBAC recommended the listing of crizotinib for the treatment of ROS1-positive locally advanced (Stage IIIB) or metastatic (Stage IV) non-small cell lung cancer (NSCLC). In making this recommendation, the PBAC acknowledged that there is a high unmet clinical need in the small proposed population (approximately ''''' patients per year, 1.6% of all patients with NSCLC), and recalled that this submission was the result of an invitation from the PBAC …PSD · Jul 2018
6.2 The PBAC noted that the MSAC had foreshadowed its support for a new MBS item for ROS1 FISH testing to inform eligibility for crizotinib treatment in this population (Public Summary Document, Application No. 1454, crizotinib, November 2017 MSAC meeting).PSD · Jul 2018
Economic analysis
5.5 In the previous major submission considered by PBAC in November 2017, the submission presented a cost-effectiveness analysis against pemetrexed. The minor re-submission did not alter the economic model structure from November 2017 but sought to respecify the best estimate of the base case ICER by addressing the PBAC’s concerns surrounding: the efficacy of the comparator, pemetrexed; the incremental effectiveness of crizotinib versus pemetrexed; …PSD · Jul 2018
The respecified base case ICER was verified by the Department. Pemetrexed efficacyPSD · Jul 2018
Clinical claim
6.24 The submission claimed that crizotinib had superior effectiveness over its main comparator, pemetrexed, in patients with ROS1-positive advanced NSCLC who have progressed on prior platinum-based chemotherapy.PSD · Nov 2017
6.25 The ESCs considered that, although crizotinib was likely to be more effective than pemetrexed, the magnitude of incremental effectiveness was difficult to estimate.PSD · Nov 2017
Consumer comments
5.2 The PBAC noted and welcomed the input from individuals (6) and organisations (1) via the Consumer Comments facility on the PBS website. The comments described benefits of treatment with crizotinib, and emphasized the effectiveness of targeted therapies like crizotinib in reducing tumour burden and improving quality of life.PSD · Jul 2018
5.3 A comment from Lung foundation Australia noted that the PBS listing of crizotinib would make a meaningful difference in the lives of the small population of ROS1- positive NSCLC patients.PSD · Jul 2018
Cost-effectiveness
The respecified base case ICER was verified by the Department. PSD · 2018
ICER uncertain ×4ICER / price too highEconomic model disputedPrice cut / RSA neededSurrogate endpointIndirect comparison
Decision context
PopulationAdults with locally advanced (Stage IIIB) or metastatic (Stage IV) non-squamous or not otherwise specified type NSCLC with ROS1 gene rearrangement (≥15% positive cells by FISH testing) and WHO performance status ≤2.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Jul 2018 | Recommended | pemetrexed | $45k–75k | Single-arm · PFS |
| Nov 2017 | Deferred | pemetrexed | — | Single-arm · PFS |
| Mar 2017 | Recommended | chemotherapy (non-exchangeable trial comparison arms) | $45k–75k | RCT · OS |
| Nov 2014 | Recommended · restricted | pemetrexed | $105k–200k | RCT · OS |
| Mar 2014 | Deferred | pemetrexed | $45k–75k | RCT · PFS |
| Nov 2013 | Recommended · restricted | pemetrexed | — | RCT · PFS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| EUCROSS | Ph 2 | 34 | Objective Response Rate (ORR); evaluation criteria: investigator assessed RECIST v.1.1 ana… | completed |
Codependent tests
| Service | Biomarker | MSAC outcome | Year |
|---|---|---|---|
| ALK gene rearrangement testing (FISH) in NSCLC | ALK gene rearrangement | supported with conditions | 2013 |
| ROS1 FISH testing for NSCLC | ROS1 gene rearrangement | supported | 2018 |
| FISH test for ALK rearrangement in NSCLC | ALK gene rearrangement | supported | 2019 |
| 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 one organisation (Lung Foundation Australia) provided input via the PBS website, describing benefits of crizotinib treatment in reducing tumour burden and improving quality of life for ROS1-positive NSCLC patients, with commentary noting this addresses significant unmet need in a small patient population.
The comments described benefits of treatment with crizotinib, and emphasized the effectiveness of targeted therapies like crizotinib in reducing tumour burden and improving quality of life. Consumer comments · PSD
quality of lifetreatment efficacyunmet needaccess to targeted therapy
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to ROS1-positive NSCLC only, excluding the TGA-approved ALK-positive indication.