The approvals of pertuzumab for metastatic breast cancer were based on a multicentre, randomised, double-blind, placebo-controlled phase III clinical trial (CLEOPATRA - WO20698) which included 808 patients with HER2-positive metastatic or locally recurrent unresectable breast cancer. Patients received either placebo, trastuzumab and docetaxel or pertuzumab, trastuzumab and docetaxel. The addition of pertuzumab to the treatment resulted in an extension of the median progression-free survival (PFS) by over 6 months (18.5 months vs 12.4 months)1,2,3. The median overall survival (OS) was 56.5 months in patients who took pertuzumab compared to 40.8 in patients who didn’t. The difference in overall response rate (ORR) was 10.8% in favour of pertuzumab (80.2% vs. 69.3%) with 5.5% complete responses (vs. 4.2%)2,3.
The approvals of pertuzumab as neoadjuvant treatment of breast cancer was based on two studies. The first, a phase II, multicentre, multinational randomised controlled trial (NEOSPHERE - WO20697) which involved 417 patients with newly diagnosed, early, inflammatory or locally advanced HER2-positive breast cancer who had not received prior trastuzumab, chemotherapy or radiotherapy. Patients were randomised to receive one of the following neoadjuvant regimens for 4 cycles prior to surgery:
- trastuzumab plus docetaxel
- Perjeta (pertuzumab) plus trastuzumab and docetaxel
- Perjeta (pertuzumab) plus trastuzumab
- Perjeta (pertuzumab) plus docetaxel2,3
The pathological complete response (pCR), defined as the absence of residual invasive disease in the breast and in the armpit lymph nodes at the completion of the neoadjuvant treatment6 was 39.3% [95% CI: 30, 49.2] in the group that took pertuzumab in combination with trastuzumab and docetaxel which was 2 to almost 4 times higher than the other combinations2,3.
The second study (TRYPHAENA - BO22280) a multicentre, randomised phase II clinical trial, involved 225 adult female patients with HER2-positive locally advanced, operable, or inflammatory breast cancer who had not received prior trastuzumab, chemotherapy or radiotherapy. Patients were randomly allocated to receive 1 of 3 neoadjuvant regimens prior to surgery as follows:
- 3 cycles of FEC (5-Fluorouracil, epirubicin, and cyclophosphamide) followed by 3 cycles of docetaxel all in combination with Perjeta (pertuzumab) and trastuzumab,
- 3 cycles of FEC alone followed by 3 cycles of docetaxel and trastuzumab in combination with Perjeta (pertuzumab)
- 6 cycles of docetaxel, carboplatin, and trastuzumab in combination with Perjeta (pertuzumab).
The highest pCR rates were achieved in the last of the three groups, with a pCR rate of 66.2% [95% CI: 54.6; 76.6] vs 61.6% [95% CI: 49.5; 72.8] and 57.3% [95% CI: 45.4; 68.7] in the first and second group, respectively2,3.