Assisting Community-Based Oncologists and Surgeons in Making Neoadjuvant Treatment Decisions for Patients with Early Breast CancerClinical trials of neoadjuvant treatment in HER2-positive disease
3:15 minutes.
TRANSCRIPTION:
DR MAMOUNAS: The 2 trials that actually were used for the accelerated approval by the FDA were the NEOSPHERE trial and the TRYPHAENA trial. So the NEOSPHERE trial was a trial that actually was more of a proof-of-principle trial that added pertuzumab to trastuzumab plus docetaxel in 1 arm. Another arm had docetaxel plus pertuzumab, as 2 drugs. And then a fourth arm in that trial had pertuzumab and trastuzumab, just to what the monoclonal antibodies by themselves will do. And essentially the trial saw a doubling of pathologic complete response when pertuzumab was added to trastuzumab plus docetaxel. Pertuzumab by itself with docetaxel was as effective as trastuzumab. The pathologic response was about 24% versus 29%. And the 2 antibodies by themselves saw about a 17% pathologic complete response rate. So there was activity even without chemotherapy to get to pathologic responses. But this was given in a short period, and then everybody went to surgery and eventually went to receive some standard adjuvant therapy, which included FEC followed by trastuzumab for the remaining of a year. So only the anthracycline was given all afterwards, but the arm that got only the 2 monoclonal antibodies also received docetaxel in the adjuvant setting. So this study showed, as a proof of principle, pertuzumab, when added to trastuzumab, improves pathologic complete response rate. And then there was a second trial, the TRYPHAENA trial, which was a 3-arm trial, more pragmatic trial, looking at different regimens of neoadjuvant chemotherapy, including anthracycline based and nonanthracycline based. So that trial had 3 arms. The first arm had TCHP times 6, so it was trastuzumab/pertuzumab/carboplatin and docetaxel for 6 cycles. The second arm had 3 cycles of FEC chemotherapy followed by THP for 3 cycles. And the third arm had trastuzumab/pertuzumab given from the beginning with FEC for 3 cycles followed by docetaxel for 3 cycles. And essentially the primary endpoint, I thought, was actually assessment of cardiotoxicity, but a secondary endpoint studied pathologic complete response. And pathologic complete response was pretty significant for all 3 arms, in the range of about 60% to 70%. And again, as we talked before, with some differences between the ER-positives and ER-negatives, where in the ER-positives was about 45% average, and the ER-negatives was I would say about 70% average. So these 2 trials were used as a foundation for accelerated approval of pertuzumab based on increase in pathologic complete response rates, with a caveat that the large adjuvant trial, the APHINITY trial, has already been completed and waiting for results in disease-free and overall survival to potentially change this to permanent approval or not, depending on how the results go. DR LOVE: So what is the APHINITY trial? What’s that looking at, Kim? DR BLACKWELL: So this is an adjuvant study. And the main question is, does adding pertuzumab to trastuzumab/anthracycline and taxane benefit patients in the adjuvant setting? And with a little over 3,000 patients, it completed its accrual now in mid 2014 to early 2014. And so it’s not clear. We’re anticipating some results, if the event rate is met, at somewhere in late 2016. |