Trifluridine With TipiracilLonsurf
Extension to current listing for treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have been previously treated with, or are not candidates for treatment with, fluoropyrimidine, platinum and either a taxane- or irinotecan-based chemotherapy and, if appropriate, HER2/neu-targeted therapy.
Decisions on record
- Meeting Mar 2018 Not recommended Indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-
- Meeting Nov 2017 Not recommended Indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents.
- Meeting Jul 2017 Not recommended LONSURF is indicated for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti- VEGF agents, and anti- EGFR agents.
- Meeting Mar 2017 Not recommended A positive TGA Delegate’s Overview was provided but the final indication of the TGA registration is not known.
Access path
- TGA registered · Lonsurf
TGA label narrower than the PBS population
- Nov 2016Not recommended
vs best supportive care
- Mar 2017Not recommended
- Jul 2017Not recommended
High and uncertain ICER, modest clinical benefits unlikely to be realised in clinical practice, insufficient rebates to…
- Nov 2017Not recommended
modest clinical benefit in the context of substantial toxicity, high and uncertain ICER, concern that the extent of…
- Mar 2018Not recommended
modest clinical benefit in context of substantial toxicity, high and uncertain ICER, base case ICER likely represents…
- ↻ resubmittedJul 2018Recommended
ICER dropped $75,000 → $45,000 (-40%)
- Nov 2019Recommended · restricted
Comparator changed: best supportive care → placebo plus best supportive care (BSC)
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended the Authority Required (STREAMLINED) listing of trifluridine/tipiracil for third (or subsequent) line treatment of patients with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction previously treated with at least two prior lines of chemotherapy that included a fluoropyrimidine, a platinum, and either a taxane- or irinotecan.PSD · Nov 2019
7.2 The PBAC considered it was not necessary to specify in the restriction that patients must have previously been treated with, if appropriate, HER2/neu-targeted therapy” in the restriction, as per the request in the submission. Rather, the PBAC considered that the use of a HER2/neu-targeted therapy in appropriate patients could be left to the judgement of the treating clinician without resulting in use outside the intended population.PSD · Nov 2019
6.35 The submission presented a trial-based cost-utility analysis based on the TAGS trial.PSD · Nov 2019
The use of a within trial analysis was appropriate given the extent of follow-up in the TAGS trial was such that most patients had died at the end of follow-up.PSD · Nov 2019
6.28 The submission claimed trifluridine/tipiracil plus BSC as superior in terms of effectiveness and inferior in terms of safety compared with BSC in patients with mG/GEJ adenocarcinoma who have failed, are intolerant of or not candidates for, standard available anticancer therapies.PSD · Nov 2019
6.29 The claim of superior effectiveness was based on the clinical evidence from the TAGS trial showing 2.1 months gain in median OS (mean 2.4 months) for trifluridine/tipiracil compared with placebo which corresponded to a HR of 0.69 (95% CI: 0.56, 0.85) of death.PSD · Nov 2019
6.2 The PBAC noted and welcomed the input from a health care professional (1) and an organisation (1) via the Consumer Comments facility on the PBS website. The comments from the health care professional noted the benefit of having an oral treatment option for patients with mG/GEJ adenocarcinoma who have limited therapeutic options available to them.PSD · Nov 2019
6.3 The PBAC noted that the Medical Oncology Group of Australia (MOGA) expressed its support for the trifluridine/tipiracil submission. The PBAC noted that the MOGA presented a European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO-MCBS) for trifluridine/tipiracil, which was limited to 3 (out of a maximum of 5, where 5 and 4 represent the grades with substantial improvement)1, based on a comparison with placebo plus BSC.PSD · Nov 2019
Cost-effectiveness
ICER value(s) not stated in the public summary document; economic evaluation section incomplete in provided text.
The PBAC considered that the base case ICER for this scenario should not exceed $50,000 per QALY gained. PBAC · 2017
Decision context
PopulationAdults with metastatic gastric adenocarcinoma, including adenocarcinoma of the gastroesophageal junction, who have received at least two prior chemotherapy regimens including a fluoropyrimidine, platinum, and either a taxane or irinotecan, with ECOG performance status 0–1, and who are refractory to or intolerant of their most recent prior therapy.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2019 | Recommended · restricted | placebo plus best supportive care (BSC) | — | RCT · OS |
| Jul 2018 | Recommended | best supportive care | $15k–45k | RCT · OS |
| Mar 2018 | Not recommended | best supportive care | $45k–75k | RCT · OS |
| Nov 2017 | Not recommended | best supportive care | $45k–75k | RCT · OS |
| Jul 2017 | Not recommended | best supportive care | $45k–75k | RCT · OS |
| Mar 2017 | Not recommended | best supportive care | $45k–75k | RCT · OS |
| Nov 2016 | Not recommended | best supportive care | — | RCT · OS |
Consumer voice
A health care professional and the Medical Oncology Group of Australia (MOGA) provided input supporting trifluridine/tipiracil for mG/GEJ adenocarcinoma, noting the benefit of an oral treatment option, good tolerability, quality of life maintenance, and clinical benefit compared to placebo plus best supportive care.
The comments from the health care professional noted the benefit of having an oral treatment option for patients with mG/GEJ adenocarcinoma who have limited therapeutic options available to them. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC requires ECOG 0–1 performance status and refractory/intolerant status; TGA label has no performance status restriction.