← The record

LenvatinibARX-Lenvatinib

Recommended HepatologyRestrictedFirst-line line 💬 consumer voice

Advanced (unresectable) Barcelona Clinic Liver Cancer stage B or stage C hepatocellular carcinoma, first-line treatment.

8
Submissions
5 resub
2015–18
On the record
$45k–75k
ICER range
3 sourced ICERs · 2016–2018
Cost-min
Cost basis
risk sharing

Decisions on record

10 decisions
  • Meeting Nov 2018 Recommended Hepatocellular carcinoma
  • Meeting Jul 2018 Recommended Locally advanced or metastatic differentiated thyroid cancer
  • Meeting Jul 2018 Deferred Hepatocellular carcinoma
  • Meeting Mar 2018 Not recommended LENVATINIB is indicated for the treatment of:  patients with progressive, locally advanced or metastatic, radioactive iodine refractory differentiated thyroid cancer.  (in combination with everolimus) adult patients with advanced renal cell carcinoma whose disease has progressed following one prio
  • Meeting Mar 2018 Not recommended Indication not stated
  • Meeting Mar 2018 Not recommended Indication not stated
  • Meeting Nov 2017 Not recommended Advanced renal cell carcinoma (RCC)
  • Meeting Jul 2016 Recommended Thyroid cancer
2 earlier decisions
  • Mar 2016 Not recommended Differentiated thyroid cancer
  • Nov 2015 Deferred Stage III or IV differentiated thyroid cancer

Access path

8 submissions · public record
  1. TGA registered · ARX-Lenvatinib

    TGA label narrower than the PBS population

  2. Nov 2015
    Deferred

    vs sorafenib and best supportive care (placebo)

  3. Mar 2016
    Not recommended

    ICER too high, eligible population sub-optimally defined, restriction not robust, estimated patient numbers…

  4. ↻ resubmitted
    Jul 2016
    Recommended

    Comparator changed: best supportive care, sorafenib → best supportive care

  5. Nov 2017
    Not recommended

    unclear clinical place in therapy given treatments currently available (nivolumab, axitinib), uncertain appropriate…

  6. Mar 2018
    Not recommended

    clinical need and clinical place in therapy not adequately established, uncertain magnitude of clinical benefit…

  7. ↻ resubmitted
    Jul 2018
    Recommended · restricted

    Comparator changed: everolimus monotherapy (primary); nivolumab (secondary); cabozantinib…

  8. Jul 2018
    Recommended · restricted

    Comparator changed: everolimus monotherapy (primary); nivolumab (secondary); cabozantinib…

  9. Nov 2018
    Recommended

    Comparator changed: best supportive care → sorafenib

  10. PBS listing · Restricted
RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
4.1 The PBAC reaffirmed its July 2018 advice that lenvatinib be listed on a cost- minimisation basis compared to sorafenib with the equi-effective doses based on the mean treatment durations and mean doses from Study 304.PSD · Nov 2018
4.2 The PBAC further recommended that it may be reasonable that the drug cost for lenvatinib be no more than 5% higher than the price of sorafenib using the previously recommended equi-effective doses reflecting its different safety profile.PSD · Nov 2018
Economic analysis
6.19 The submission presented a cost-minimisation analysis for lenvatinib compared with sorafenib. The submission assumed that there were no differences in resource use between lenvatinib and sorafenib other than the use of the drugs themselves.PSD · Jul 2018
6.20 The submission based the equi-effective dose on the median lenvatinib daily dose and duration from Study 304. Treatment exposure for sorafenib was estimated from the median sorafenib daily dose in Study 304 and the median treatment duration from the PBS 10% Population Sample.PSD · Jul 2018
Clinical claim
6.16 The submission described lenvatinib as non-inferior in terms of effectiveness compared with sorafenib. This was consistent with the non-inferiority result for OS.PSD · Jul 2018
The submission also described lenvatinib as superior in terms of OS based on subgroup analyses of the full-analysis set (FAS) in patients with baseline alpha- fetoprotein levels ≥ 200 ng/mL. The evaluators considered that this claim may not be supported given the post-hoc nature of the sub-group analysis. The pre-PBAC response stated that this analysis was pre-planned to adjust for other variables which may have impacted OS.PSD · Jul 2018
Consumer comments
3.10 There were no consumer comments received for this item. Equi-effective dose and corresponding pricePSD · Nov 2018
3.13 At the July 2018 meeting, the PBAC considered that it is appropriate for the equi- effective doses to be based on the mean estimates of dose and duration from Study 304 as these estimates appropriately capture the range of doses and treatment durations, and reflect the range likely in clinical practice. The use of the medians will result in an underrepresentation of patients who remain on treatment for a relatively long duration.PSD · Nov 2018

Cost-effectiveness

3 sourced ICERs · 2016–2018

Cost-minimisation analysis; no ICER calculated as lenvatinib and sorafenib are cost-equivalent on an equi-effective dose basis.

The PBAC considered that a cost-minimisation analysis was reasonable when the mean treatment durations and mean doses of lenvatinib and sorafenib were used so that the treatment cost per patient was the same for both treatments. PBAC · 2018
ICER uncertainICER / price too highEconomic model disputedPrice cut / RSA neededCost-effectiveness accepted ×2

Decision context

PopulationPatients with advanced (unresectable) Barcelona Clinic Liver Cancer stage B or stage C hepatocellular carcinoma, who are not suitable for transarterial chemoembolisation, have WHO performance status ≤2, are Child-Pugh class A, and have not received prior VEGF tyrosine kinase inhibitor therapy or have developed intolerance necessitating permanent withdrawal.

Risk sharingRisk-share arrangement including a financial cap in place for lenvatinib 4 mg (30 tablets). The PBAC further recommended that the drug cost for lenvatinib be no more than 5% higher than sorafenib using the previously recommended equi-effective doses.

Submission history

8 entries
DecidedOutcomeComparatorICEREvidence
Nov 2018 Recommended sorafenib RCT · OS
Jul 2018 Recommended · restricted sorafenib RCT · OS
Jul 2018 Recommended · restricted best supportive care Other
Mar 2018 Not recommended everolimus monotherapy (primary); nivolumab (secondary); cabozantinib and axitinib (supplementary) $45k–75k RCT · OS
Nov 2017 Not recommended everolimus monotherapy RCT · PFS
Jul 2016 Recommended best supportive care $45k–75k RCT · Other
Mar 2016 Not recommended best supportive care, sorafenib $45k–75k RCT · PFS
Nov 2015 Deferred sorafenib and best supportive care (placebo) RCT · PFS

Consumer voice

Jul 2018

No consumer comments were received for this item.

The PBAC noted that no consumer comments were received for this item. Consumer comments · PSD

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to BCLC stage B/C, excludes prior VEGF-TKI, requires PS ≤2 and Child-Pugh A; TGA label has no such restrictions.