RegorafenibStivarga
Treatment of patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered suitable candidates for, fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, anti-VEGF therapy, and if RAS wildtype, anti-EGFR therapy.
Decisions on record
- Meeting Nov 2021 Not recommended Colorectal cancer (metastatic)
- Meeting Jul 2019 Not recommended The treatment of patients with hepatocellular carcinoma (HCC) who have been previously treated with sorafenib.
- Meeting Nov 2018 Not recommended REGORAFENIB is indicated for the treatment of patients with: Metastatic colorectal cancer who have been previously treated with fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapy, an anti-VEGF therapy, and, if RAS wild type, an anti-EGFR therapy. Unresectable or metastatic gastroi
- Meeting Nov 2018 Not recommended Indication not stated
- Meeting Mar 2018 Not recommended Hepatocellular carcinoma (HCC)
- Meeting Mar 2015 Not recommended Gastrointestinal stromal tumours
- Meeting Jul 2014 Not recommended Bayer Australia Ltd New listing (Major submission) Metastatic colorectal cancer (mCRC) Authority required (Streamlined) listing for treatment of patients with metastatic colorectal cancer (mCRC) who have a WHO performance status of 0 or 1, following failure of or intolerance to prior therapy. the im
Access path
- TGA registered · Stivarga
TGA label narrower than the PBS population
- Jul 2014Not recommended
vs best supportive care (BSC)
- Mar 2015Not recommended
Comparator changed: best supportive care (BSC) → best supportive care
- Mar 2018Not recommended
Comparator changed: best supportive care → best supportive care (BSC)
- Nov 2018Not recommended
Comparator changed: best supportive care (BSC) → best supportive care
- Jul 2019Not recommended
- Nov 2021Not recommended
Comparator changed: best supportive care → trifluridine/tipiracil
From the public summary
The PBAC did not recommend the listing of regorafenib for the treatment of metastatic colorectal cancer (mCRC) after treatment with two or more prior therapies, on the basis that the evidence presented indicated regorafenib is toxic and would adversely impact patients’ overall quality of life, whilst having a limited impact on prognosis.PSD · Nov 2021
The PBAC noted there appeared to be limited support amongst clinicians or patients for the PBS listing of regorafenib in this population, given only one comment was received, from Bowel Cancer Australia, which was in general support for additional choices for patients. The Committee also noted the Medical Oncology Group of Australia (MOGA) did not include regorafenib in its list of supported applications.PSD · Nov 2021
Economic evaluation The PBAC considered that use of regorafenib A cost minimisation to trifluridine/tipiracil was associated with an unacceptably high ICER was presented based on indirect (para 7.8, July 2014 PSD). comparison.PSD · Nov 2021
Inclusion of cost The ESC considered that the cost of adverse The resubmission did not include the associated with the events was likely to be underestimated as the costs for the management and management and model does not include palliative care costs or monitoring of adverse events. monitoring of adverse costs associated with adverse events that require events hospitalisation (para 6.22, July 2014 PSD).PSD · Nov 2021
The resubmission described regorafenib as non-inferior in terms of effectiveness compared to trifluridine/tipiracil. The evaluation identified the key issues of uncertainty with this claim were: The lack of a statistically significant difference in the primary outcome in the indirect comparison is not sufficient to establish non-inferiority in the absence of a non-inferiority margin; andPSD · Nov 2021
1 T. J., Jacobs, N. L., Pasche, B. C., Cleary, J. M., Meyers, J. P., Desnoyers, R. J., McCune, J. S., Pedersen, K., Barzi, A., Chiorean, E. G., Sloan, J., Lacouture, M. E., Lenz, H. J., & Grothey, A. (2019). Regorafenib dose-optimisation in patients with refractory metastatic colorectal cancer (ReDOS): a randomised, multicentre, open-label, phase 2 study. The Lancet. Oncology, 20(8), 1070–1082. https://doi.org/10.1016/S1470-2045(19)30272-4PSD · Nov 2021
The PBAC noted and welcomed the input from Bowel Cancer Australia which broadly supported the application to increase choices for patients.PSD · Nov 2021
There is currently a Special Pricing Arrangement and a Risk sharing Agreement in place for trifluridine/tipiracil in the mCRC therapeutic area.PSD · Nov 2021
Cost-effectiveness
Cost minimisation approach versus trifluridine/tipiracil; no numeric ICER stated in this excerpt
Decision context
PopulationAdults with metastatic colorectal cancer who have previously failed or are unsuitable for fluoropyrimidine, oxaliplatin, irinotecan-based chemotherapy, anti-VEGF therapy, and if RAS wildtype, anti-EGFR therapy, with WHO performance status ≤1
Risk sharingRegorafenib joining existing trifluridine/tipiracil risk sharing arrangement (RSA) to manage risk of leakage to patients with WHO performance status >1 and sequential use beyond third line
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2021 | Not recommended | trifluridine/tipiracil | — | Meta-analysis · OS |
| Jul 2019 | Not recommended | best supportive care | $45k–75k | RCT · OS |
| Nov 2018 | Not recommended | best supportive care | — | RCT · OS |
| Mar 2018 | Not recommended | best supportive care (BSC) | — | RCT · OS |
| Mar 2015 | Not recommended | best supportive care | — | RCT · PFS |
| Jul 2014 | Not recommended | best supportive care (BSC) | $45k–75k | RCT · OS |
Clinical evidence
Consumer voice
No consumer comments were received for this item. The Medical Oncology Group of Australia expressed strong support for regorafenib as a high-priority PBS listing based on the RESORCE trial, presenting an ESMO-MCBS score of 3 out of 5.
The PBAC noted that no consumer comments were received for this item. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC adds WHO performance status ≤1 restriction and explicitly includes 'unsuitable candidates' alongside 'previously treated' patients.