28 April 2022  The rejection of dostarlimab should not come as a surprise, the rejection of sotorsaib less so.

Dostarlimab

The PBAC did not recommend the PBS listing of dostarlimab for the treatment of patients with recurrent or advanced mismatch repair deficient endometrial cancer who have disease progression following prior systemic therapy. 

The Committee noted that the clinical evidence submitted for dostarlimab was based on a relatively small single-arm study (GARNET) with immature follow-up and considered there were key transitivity and methodological issues with the indirect comparisons presented in the submission.

Overall, the PBAC considered that the magnitude of benefit for dostarlimab over chemotherapy was uncertain and the incremental cost effectiveness ratio was highly uncertain because the modelled survival benefit was not adequately supported by the available data.

Dostarlimab has already been assessed by other HTA agencies:

• England (NICE) - just scraped through with a draft recommendation to be listed in the Cancer Drugs Fund. NICE also had issues with the indirect comparison. The Appraisal Committee concluded that evidence from the real world data sub-group was not a robust comparator for GARNET.
• France (Transparency Commission) - Insufficient. The Transparency Commission concluded that in the current state of the data, dostarlimab has no place in the therapeutic strategy. It considered that, in the context where no robust comparative data are available to guarantee the solidity of the conclusion on the effect of treatment with dostarlimab, the introduction of this medicinal product into the therapeutic strategy would be accompanied by greater risk-taking than for medicines whose effectiveness is based on a comparison made with a risk control of incorrectly concluding that the treatment is effective (alfa risk commonly accepted at 5% bilaterally).
• Germany (IQWiG/G-BA) - No additional clinical benefit. The analyses presented by GSK for the comparison of individual arms of different studies were deemed to be unsuitable for the assessment. IQWIG based its rationale on the fact that the data on the mismatch repair deficient or microsatellite instability-high status of the patients is missing in the comparator studies. Thus, the similarity of the patients with those in the single-arm GARNET study submitted for dostarlimab could not be examined.

Sotorasib

The PBAC decided not to recommend sotorasib for the treatment of patients with non-squamous or NOS stage IIIB (locally advanced) or stage IV (metastatic) non-small-cell lung cancer who harbour the KRAS G12C variant and who have progressed on prior therapy.

The Committee considered it was likely that sotorasib provided some clinical benefit over docetaxel but the magnitude of the benefit was highly uncertain.

The PBAC considered the incremental cost effectiveness ratio was uncertain and unacceptably high at the proposed price.

Sotorasib has been already been assessed by NICE and the SMC:

• England (NICE) - Recommended for listing in the Cancer Drugs Fund. The Appraisal Committee acknowledged that the clinical evidence from the CodeBreaK100 study is relevant and concluded that he indirect treatment comparisons show a survival benefit for sotorasib when compared with docetaxel and nintedanib esylate and docetaxel.
• Scotland (SMC) - accepted for use on an interim basis by NHS Scotland subject to on-going evaluation and future reassessment.