Trastuzumab; Pertuzumab; Trastuzumab Emtansine
Trastuzumab: first-line and second/later-line treatment of HER2-positive metastatic breast cancer. Pertuzumab: first-line treatment in combination with trastuzumab and docetaxel for HER2-positive metastatic breast cancer. Trastuzumab emtansine (T-DM1): second-line treatment for HER2-positive metastatic breast cancer previously treated with trastuzumab and a taxane.
Access path
- Nov 2014Recommended · restricted
vs Trastuzumab first-line: docetaxel; Trastuzumab…
- PBS listing · Authority Required
From the public summary
7.1 The PBAC recommended the listing of pertuzumab under Section 100 (Efficient Funding of Chemotherapy Drugs Program) for the treatment of HER2 positive metastatic breast cancer in combination with trastuzumab and a taxane in the first- line setting.PSD · Nov 2014
7.2 The PBAC recommended extending the listing of trastuzumab under Section 100 (Efficient Funding of Chemotherapy Drugs Program) for the treatment of HER2 positive metastatic breast cancer in the first-line setting as well as in patients whose disease has progressed despite treatment with trastuzumab for metastatic disease.PSD · Nov 2014
6.29 Trastuzumab first-line: the structure of the economic evaluation remained unchanged from the previous submission. The key differences to the inputs are described in the table below. 15PSD · Nov 2014
6.30 Trastuzumab second-line: a new ‘Area under the curve (AUC)’ model was presented.PSD · Nov 2014
6.22 Trastuzumab first-line: the resubmission made no new claims with regards to trastuzumab in first-line therapy with respect to efficacy and safety. However, PBAC has previously accepted the following claims (PBAC Ratified Minutes, trastuzumab, 2008): combined therapy with trastuzumab plus taxanes (docetaxel or paclitaxel) is more effective, but associated with greater toxicity, than taxanes alone as a first- line treatment for MBC; dual therapy …PSD · Nov 2014
6.23 Trastuzumab second- and later-lines: the resubmission described trastuzumab as superior in terms of response rates, PFS and OS in patients who have continued trastuzumab after disease progression compared with those who have not, and the safety profile in later-line therapy is comparable to the trastuzumab and lapatinib arms of GBG-26 and EGF100151 (Cameron 2010) (treatment in second-line). The 14PSD · Nov 2014
6.2 The PBAC noted and welcomed the input from individuals (4), health care professionals (5) and organisations (1) via the Consumer Comments facility on the PBS website relating to pertuzumab. The comments described a range of benefits of treatment with pertuzumab including the ability to live a healthy and active life with minimal impact from continuing treatment, prolonging survival and increasing quality of life.PSD · Nov 2014
6.3 The PBAC noted and welcomed the input from individuals (9), health care professionals (9) and organisations (1) via the Consumer Comments facility on the PBS website relating to trastuzumab emtansine. The comments described a range of benefits of treatment with trastuzumab emtansine including improvements in quality of life, reduced side effects and improved prognosis.PSD · Nov 2014
Cost-effectiveness
Multiple ICERs reported across different indications and comparators. Trastuzumab first-line: $45,000–$75,000/QALY. Trastuzumab later-lines: $105,000–$200,000/QALY (GBG 26) and $45,000–$75,000/LYG (Berghoff). T-DM1 ICER not numerically stated in public text (redacted).
The resubmission presented Berghoff (2013): an observational study comparing multiple-line and single-line treatment with trastuzumab to no treatment with trastuzumab (n=201). PSD · 2014
Decision context
PopulationTrastuzumab first-line: patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy for metastatic disease. Trastuzumab second/later-lines: patients with HER2-positive metastatic breast cancer whose disease has progressed despite prior trastuzumab therapy. Pertuzumab: patients with HER2-positive metastatic breast cancer who have not received prior anti-HER2 therapy or chemotherapy, performance status 0–1, in combination with trastuzumab and docetaxel. T-DM1: patients with HER2-positive metastatic breast cancer who have received prior trastuzumab and a taxane and whose disease has progressed.
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Nov 2014 | Recommended · restricted | Trastuzumab first-line: docetaxel; Trastuzumab second/later-lines: capecitabine; Pertuzumab: trastuzumab + taxane; T-DM1 | $45k–200k | RCT · OS |
Clinical evidence
| Trial | Phase | N | Primary outcome | Status |
|---|---|---|---|---|
| CLEOPATRA | Ph 3 | 808 | Progression-Free Survival (PFS) Determined by an Independent Review Facility | completed |
Consumer voice
Consumer input from individuals, healthcare professionals and organisations described benefits of pertuzumab and trastuzumab emtansine including improved quality of life, prolonged survival and reduced side effects, while noting the financial stress families experience when paying for these treatments privately.
the ability to live a healthy and active life with minimal impact from continuing treatment Consumer comments · PSD
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts trastuzumab to first/second-line and pertuzumab to first-line; TGA permits broader use including aromatase inhibitor combinations not addressed in PBAC assessment.