Trastuzumab EmtansineKadcyla
Adjuvant treatment of patients with HER2-positive early breast cancer who have residual disease after pre-operative systemic treatment that included HER2-targeted therapy.
Decisions on record
- Meeting Nov 2019 Recommended Early breast cancer
- Meeting Nov 2014 Deferred 100 mg injection, 1 x 100 mg vial, 160 mg injection, 1 x 160 mg vial; Kadcyla®, Roche Products Pty Ltd New Listing (Major submission) HER2 positive metastatic breast cancer Section 100 listing for trastuzumab emtansine (T-DM1) for treatment of a patient with HER2+ metastatic breast cancer who has re
- Meeting Mar 2014 Deferred Kadcyla® Roche Products Pty Limited Breast Cancer The resubmission requests a Section 100 (Efficient Funding of Chemotherapy Drugs program) Authority Required listing for the treatment of patients with HER2 positive metastatic breast cancer (stage IV) who have received prior therapy with trastuzumab
- Meeting Jul 2013 Not recommended Breast cancer
Access path
- TGA registered · Kadcyla
TGA label equal than the PBS population
- Jul 2013Not recommended
vs lapatinib + capecitabine
- Mar 2014Deferred
Comparator changed: lapatinib + capecitabine → lapatinib plus capecitabine
- Nov 2019Recommended
Comparator changed: lapatinib plus capecitabine → trastuzumab
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended the listing of T-DM1 for the treatment of adjuvant therapy of patients with HER2 positive eBC with residual disease following HER2-targeted neoadjuvant therapy that included trastuzumab and taxane-based chemotherapy.PSD · Nov 2019
The PBAC acknowledged the high clinical need of patients in this population. The PBAC is satisfied that T-DM1 provides, for some patients, a significant improvement in iDFS over trastuzumab. Although the data for OS were immature, the PBAC considered that there was moderate certainty that the iDFS results would translate into OS benefits based on the KATHERINE trial data.PSD · Nov 2019
6.27 The submission presented a stepped economic evaluation based on KATHERINE and implemented a modelled cost-effectiveness analysis (CEA) and cost-utility analysis (CUA) for T-DM1 vs. trastuzumab. Health benefits were reported as life years gained (LYGs) and quality adjusted life years (QALYs) gained, respectively. The latest iDFS data were used for the economic analysis (cut-off 25th July 2018).PSD · Nov 2019
Outcomes LYG, QALY Markov model, extrapolated from median point of follow-up from KATHERINE (41.2 Methods used to generate results months) using the exponential parametric function applied to the iDFS data.PSD · Nov 2019
6.23 The submission described T-DM1 as superior in terms of effectiveness and inferior in terms of safety compared to trastuzumab. The commentary considered that the clinical claim was supported by the evidence with respect to iDFS, but not OS.PSD · Nov 2019
Previously, the ESC noted that a statistically significant difference in iDFS is difficult to interpret in the absence of a difference in OS (Neratinib PSD, March 2019, paragraph 6.37); however the ESC noted that this was in the context of a poorer quality trial and a considerably smaller absolute benefit in iDFS.PSD · Nov 2019
6.4 The Medical Oncology Group of Australia (MOGA) and its Breast Cancer Expert Group also expressed strong support for the T-DM1 submission, categorising it as one of the therapies of “highest priority for PBS listing” on the basis of improved disease free survival in the KATHERINE trial, but noting that the OS benefit was immature.PSD · Nov 2019
6.55 The submission did not propose any risk sharing arrangements (RSA). There are caps in place for pertuzumab and T-DM1. The pertuzumab cap is being consistently exceeded (by approximately '''''% in the most recent deed year), but the T-DM1 caps are not being reached. The PBAC considered that an RSA would be required to manage the uncertainties with the financial estimates, with '''''''% rebates beyond estimated use.PSD · Nov 2019
Cost-effectiveness
ICER value not stated in the provided text; economic analysis section appears to be cut off at Table 10 reference
The PBAC noted that this was different from the previous submission, which used a mixed comparator of lapatinib plus capecitabine, trastuzumab plus chemotherapy, and, trastuzumab monotherapy. PBAC · 2014
Decision context
PopulationPatients with HER2-positive early breast cancer who have residual invasive disease in the breast and/or axillary lymph nodes after neoadjuvant therapy that included trastuzumab and taxane-based chemotherapy
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2019 | Recommended | trastuzumab | — | RCT · PFS |
| Mar 2014 | Deferred | lapatinib plus capecitabine | — | RCT · OS |
| Jul 2013 | Not recommended | lapatinib + capecitabine | — | RCT · PFS |
Consumer voice
Nine health care professionals and organisations submitted supportive comments on T-DM1 as adjuvant treatment in early breast cancer, highlighting significant improvements in disease-free survival for HER2-positive patients with poor neoadjuvant chemotherapy response and noting expectations for improved overall survival.
The comments noted the significant improvement in disease-free survival for patients with HER2 positive eBC who have a poor response to neoadjuvant chemotherapy as demonstrated in the KATHERINE trial. Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label equal than PBS population — Both require HER2-positive early breast cancer with residual disease after neoadjuvant taxane and trastuzumab-based therapy.