← The record

SorafenibNEXAVAR

Deferred OncologyAuthority RequiredSecond-line line 💬 consumer voice

Treatment of locally advanced or metastatic, radioactive iodine refractory differentiated thyroid cancer (RAI-R DTC).

9
Submissions
7 resub
2006–15
On the record
$15k–75k
ICER range
5 sourced ICERs · 2006–2013
Redacted
Cost basis

Decisions on record

8 decisions
  • Meeting Nov 2015 Deferred Differentiated thyroid cancer
  • Meeting Mar 2015 Deferred Radioactive iodine refractory differentiated thyroid cancer
  • Meeting Nov 2014 Recommended tablet, 200 mg, Nexavar® Bayer Australia Ltd Change to listing (Minor submission) Renal cell carcinoma Extend the current Authority Required listing to include the treatment of stage IV clear cell variant renal cell carcinoma (advanced RCC) in patients who have failed first line treatment.
  • Meeting Jul 2014 Not recommended Bayer Australia Ltd Change to listing (Major submission) Thyroid Cancer Authority required listing for the treatment of patients with locally advanced or metastatic, progressive, differentiated thyroid carcinoma refractory to radioactive iodine. On the basis of the direct evidence presented by the s
  • Meeting Nov 2013 Not recommended 200mg, tablet Nexavar® Bayer Australia Limited Major submission Advanced hepatocellular carcinoma Advanced renal cell carcinoma Authority required (Streamlined) listing for treatment of Advanced Barcelona Clinic Liver Cancer Stage C hepatocellular carcinoma Listing Requested: The re-submission reque
  • Meeting Nov 2012 Not recommended Treatment advanced hepatocellular carcinoma. Treatment of advanced renal cell carcinoma.
  • Meeting Jul 2008 Recommended Liver cancer
  • Meeting Nov 2006 Not recommended Treatment for renal cell carcinoma

Access path

9 submissions · public record
  1. TGA registered · NEXAVAR

    TGA label narrower than the PBS population

  2. Nov 2006
    Recommended

    vs placebo for best supportive care

  3. Jul 2008
    Recommended · restricted

    Comparator changed: placebo for best supportive care → placebo/best supportive care

  4. Nov 2012
    Recommended

    Comparator changed: placebo/best supportive care → placebo/best supportive care (BSC)

  5. Nov 2012
    Recommended

    Comparator changed: placebo/best supportive care → placebo/best supportive care (BSC)

  6. Nov 2013
    Not recommended

    inadequate evidence of proven superior efficacy over BSC, invalid indirect comparison methodology, unequivalent common…

  7. Jul 2014
    Not recommended
  8. ↻ resubmitted
    Nov 2014
    Recommended

    Comparator changed: best supportive care → everolimus

  9. Mar 2015
    Deferred

    Comparator changed: everolimus → best supportive care

  10. Nov 2015
    Deferred

    Comparator changed: best supportive care → best supportive care (placebo)

RecommendedDeferredNot recommended

From the public summary

Verbatim · PSD text · may span indications
PBAC outcome
7.1 The PBAC deferred its decision on sorafenib for the treatment of locally advanced or metastatic RAI-R DTC as the re-submission had not provided a reliable estimate of the cost-effectiveness of sorafenib in this setting, and wished to see the results of its preferred re-specifications for the base case of the economic model.PSD · Nov 2015
9.12 months (0.76 years) estimated by the modelled economic evaluation was implausibly large. 12PSD · Nov 2015
Economic analysis
6.15 The re-submission presented a cost-utility analysis. The economic evaluation was largely unchanged from the March 2015 re-submission. The key changes were: the assumed duration of treatment was reduced to 13.44 months in Scenario 1 (it remained at 17.55 months for Scenario 2), the dispensed price of sorafenib was reduced to an effective price of $''''''''''''''''''''' in Scenario 1 and $''''''''''''''''''' in Scenario 2, and the adjusted HR for OS …PSD · Nov 2015
6.16 The key driver for the economic model was the OS benefit with sorafenib over BSC.PSD · Nov 2015
Clinical claim
6.14 The re-submission described sorafenib as superior in terms of comparative effectiveness and inferior in terms of comparative safety over BSC.  The PBAC has previously accepted the claim of superiority for PFS, but not for OS. The PBAC noted the magnitude of benefit in terms of extension of life derived from sorafenib is difficult to ascertain due to crossover following progression.PSD · Nov 2015
Consumer comments
6.2 The PBAC welcomed the input from an organisation (1) via the Consumer Comments facility on the PBS website. The comment described that there are patients who are willing to accept moderate to severe toxicities of cancer treatment to delay disease progression and that there was a need for better understanding and support for DTC.PSD · Nov 2015
Financial management – risk sharing
6.26 The submission requested an effective DPMQ of $'''''''''''''''''''' ($''''''''''''''''''') for Scenario 1 and $'''''''''''''''''''''' ($''''''''''''''''''') for Scenario 2 compared with a published DPMQ of $''''''''''''''''''''. The effective DPMQ was used in the economic evaluation and financial estimates in the re-submission.PSD · Nov 2015
6.27 The sponsor agreed to a Risk Sharing Arrangement in general, however, requested the financial cap and level of rebate be finalised following a positive recommendation by the PBAC.PSD · Nov 2015

Cost-effectiveness

5 sourced ICERs · 2006–2013

ICER values are redacted (marked as '$''''''''''''''''' /QALY'). The document indicates cost-effectiveness was assessed but specific numeric values are commercial-in-confidence.

The PBAC agreed with the ESC that it was not reasonable to attach utilities to the post-progression health state as it may result in bias against BSC. PBAC · 2015
ICER uncertain ×2ICER / price too highEconomic model disputed ×3Surrogate endpoint ×3Indirect comparisonCost-effectiveness accepted

Decision context

PopulationPatients with locally advanced or metastatic radioactive iodine-refractory differentiated thyroid cancer who have progressed after radioactive iodine treatment.

Why it was knocked back

  • ICER not reliably estimated; economic model based on uncertain overall survival data confounded by substantial crossover (71% of placebo patients crossed over); unadjusted OS did not show statistically significant improvement (HR 0.80, 95% CI 0.54–1.19); restriction did not adequately define high-risk patients aged less than 45 years as previously requested by PBAC

Submission history

9 entries
DecidedOutcomeComparatorICEREvidence
Nov 2015 Deferred best supportive care (placebo) RCT · PFS
Mar 2015 Deferred best supportive care RCT · PFS
Nov 2014 Recommended everolimus RCT · OS
Jul 2014 Not recommended best supportive care RCT · PFS
Nov 2013 Not recommended best supportive care $15k–45k RCT · OS
Nov 2012 Recommended placebo/best supportive care (BSC) $45k–75k RCT · OS
Nov 2012 Recommended placebo/best supportive care (BSC) $45k–75k RCT · OS
Jul 2008 Recommended · restricted placebo/best supportive care $45k–75k RCT · OS
Nov 2006 Recommended placebo for best supportive care $45k–75k RCT · OS, PFS

Clinical evidence

Trials cited in the PSDs · ClinicalTrials.gov
TrialPhaseNPrimary outcomeStatus
INTORSECT Ph 3 512 Progression-Free Survival (PFS) completed
RECORD-1 Ph 3 416 Progressive Free Survival (PFS) in Patients Who Receive RAD001 Plus Best Supportive Care(B… completed

Consumer voice

Nov 2015

One consumer organisation provided input describing that patients with cancer are willing to accept moderate to severe treatment toxicities to delay disease progression, and that there is a need for better understanding and support for DTC (likely dedicated treatment centre or similar).

there are patients who are willing to accept moderate to severe toxicities of cancer treatment to delay disease progression Consumer comments · PSD
treatment burdenside effectsunmet needaccess barriers

Similar precedents

By decision profile

Regulatory · TGA

Label narrower than PBS population — PBAC restricts to second-line treatment after prior radioactive iodine progression; TGA label does not specify treatment line.