Nivolumab Plus Ipilimumab
First-line treatment of previously untreated Stage IV (metastatic) non-small cell lung cancer (NSCLC) in patients without EGFR or ALK gene rearrangements, in combination with platinum-based doublet chemotherapy.
Decisions on record
- Meeting Dec 2023 Deferred Multiple indications with current or future TGA registration no PSD
- Meeting Nov 2022 Recommended Stage III or IV malignant melanoma in patients with disease recurrence after adjuvant PD-1 inhibitor
Access path
- Nov 2020Recommended · restricted
vs pembrolizumab plus platinum-based doublet chemotherapy
- PBS listing · Restricted
From the public summary
The PBAC recommended the listing of nivolumab plus ipilimumab in combination with two cycles of platinum-based doublet chemotherapy (NIVO+IPI+platinum) for the treatment of previously untreated Stage IV non-small cell lung cancer (NSCLC), limited to the squamous population only, on the basis that it should be available only under special arrangements under section 100.PSD · Nov 2020
The PBAC did not consider there to be an unmet clinical need for NIVO+IPI+platinum, as there are currently PBS listed immunotherapies to treat patients with previously untreated stage IV NSCLC. The PBAC considered NIVO+IPI+platinum may provide some patients with a treatment option with less cycles of chemotherapy but noted this perceived benefit would need to be balanced by the ongoing use of ipilimumab. 32PSD · Nov 2020
The submission presented a cost minimisation analysis (CMA) of NIVO+IPI+platinum versus pembrolizumab+platinum. The ESC considered that the claim of non-inferior comparative effectiveness was not adequately supported for patients with non- squamous NSCLC and therefore a CMA was not appropriate for this population which the submission estimated accounted for 77.6% of the total population.PSD · Nov 2020
The key components of the CMA are presented in Table 11. The equi-effective doses were based on the doses and the truncated mean duration of treatment used in the 22PSD · Nov 2020
The submission described NIVO+IPI+platinum as non-inferior in terms of both effectiveness and safety compared to pembrolizumab+platinum. The evaluation considered that while the claim that NIVO+IPI+platinum was non-inferior to pembrolizumab+platinum in terms of comparative safety was reasonable, the claim regarding the comparative effectiveness was not adequately supported: For the comparison of CM9LA (non-squamous and squamous NSCLC) and KN189 …PSD · Nov 2020
The indirect comparison was likely to be confounded by this difference in the duration of follow-up between the trials; o The indirectly derived HR for OS based on the ITT populations of the trials wasPSD · Nov 2020
The PBAC noted and welcomed the input from three organisations via the Consumer Comments facility on the PBS website. The comments described a range of benefits of treatment with NIVO+IPI+platinum including fewer side effects related to reduced cycles of chemotherapy.PSD · Nov 2020
The Medical Oncology Group of Australia (MOGA) also expressed its support for the NIVO+IPI+platinum submission. The PBAC noted that the MOGA presented a European Society for Medical Oncology Magnitude of Clinical Benefit Scale (ESMO- MCBS) for NIVO+IPI+platinum, which was limited to 4 (out of a maximum of 5, where 5 and 4 represent the grades with substantial improvement), based on a comparison with platinum-based chemotherapy†.PSD · Nov 2020
Cost-effectiveness
Cost-minimisation analysis; no ICER calculated by design.
The submission presented a cost minimisation analysis (CMA) of NIVO+IPI+platinum versus pembrolizumab+platinum. PSD · 2020
Decision context
PopulationAdults with previously untreated Stage IV (metastatic) NSCLC without EGFR or ALK gene rearrangements, ECOG performance status 0 or 1, treated with nivolumab plus ipilimumab in combination with two cycles of platinum-based doublet chemotherapy.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2020 | Recommended · restricted | pembrolizumab plus platinum-based doublet chemotherapy | — | RCT · OS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| CheckMate 9LA | Ph 3 | 719 | Overall Survival (OS) | completed |
Consumer voice
Three consumer organisations provided input describing benefits of NIVO+IPI+platinum treatment including fewer chemotherapy-related side effects and the importance of additional treatment options for NSCLC patients. The Medical Oncology Group of Australia also expressed support for the submission.
The comments described a range of benefits of treatment with NIVO+IPI+platinum including fewer side effects related to reduced cycles of chemotherapy. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to Stage IV metastatic only and requires ECOG 0-1 performance status; TGA label includes recurrent NSCLC without performance status limits.