Data Review and Key Insights: The FeDeriCa Trial and PHranceSCa Study

Dr. Joyce O’Shaughnessy briefly reviews and provides insights into the FeDeriCa and the PHranceSCa studies.

Joyce O’Shaughnessy, MD: The FeDeriCa trial was a registrational trial for the subcutaneous trastuzumab and pertuzumab, and the trial design was that patients with newly diagnosed early-stage HER2-positive breast cancer who were candidates for preoperative therapy with chemotherapy, trastuzumab and pertuzumab were randomized to standard chemotherapy plus IV trastuzumab and pertuzumab versus the subcutaneous formulation of trastuzumab and pertuzumab. About 250 patients in both arms. The primary endpoint was the trough levels of pertuzumab right before cycle 8 of the chemotherapy, trastuzumab and pertuzumab. A secondary endpoint was the trough levels of the trastuzumab right before cycle 8 comparing the subcutaneous and the IV formulations to make sure that over time, the steady-state levels of these two important antibodies were no different between the subcutaneous and IV formulation. Then another secondary endpoint was the pathologic complete response rate on the two arms of the trial. The primary and secondary endpoints were all very favorable. There was really no statistically significant difference in the trough levels of pertuzumab and trastuzumab comparing the IV and the subcutaneous, so the pharmacokinetics are the same with the IV and the subcu and the pathologic complete response rates were just a teeny bit shy of 60%. They were exactly the same on both arms, 60% so very, very reassuring, really excellent anti-tumor activity getting 60% path CR. Very, very reassuring data that pharmacokinetic-wise, steady-state levels, and efficacy, safety, really identical with both the IV and the subcutaneous formulations.

The PHranceSCA study was a very well-done trial for patients with early-stage HER2-positive breast cancer, where these patients had received preoperative chemotherapy, trastuzumab, and pertuzumab, then they had their surgery. And if these patients had a pathologic complete response, they were then candidates to finish up their year of trastuzumab and pertuzumab with endocrine therapy if they were a hormone receptor-positive. And in the PHranceSCA study and the adjuvant setting postoperatively patients were randomized to three cycles of IV trastuzumab/pertuzumab versus three cycles of subcutaneous trastuzumab/pertuzumab followed by three more cycles after that of the opposite formulation. So if they received IV for the first three cycles than they received subcu for the second three cycles and vice versa, and patients were then asked which they preferred the IV or the subcutaneous formulation, and furthermore, they were given the option of choosing, do they want the IV, or do they want the subcutaneous formulation to finish up their year of trastuzumab and pertuzumab and overwhelming patients were in favor they preferred the subcutaneous formulation about 85% of patients said they preferred and generally strongly preferred the subcutaneous formulation and then chose that even a little higher, I think, close to 90% of the patients chose the subcutaneous formulation going forward to finish up their year of trastuzumab and pertuzumab. And basically, it was time saved was the reason because the subcutaneous formulation is just administered over five minutes to 10 minutes subcutaneously. And then there's a bit of observational period afterwards, as opposed to the IV formulation, which takes a couple of hours to get the IV formulation administered. So basically it was time saved. Patients said they were also more comfortable. They didn't have to have the portacath accessed. The subcutaneous was just more comfortable physically for them, but basically, it was time saved. That's certainly been my experience as well when I offer patients the subcutaneous formulation. They're excited to hear about it Oh, great I didn't know about that. Sign me up. So the patients are excited to save time and not have to have the IV formulation. Our infusion centers are busy and there's often a wait to have your turn to have your infusion. And the subcutaneous just cuts the time down. It doesn't require the pharmacist to mix to formulate the IV administration of trastuzumab and pertuzumab. It just comes in a fixed dose combination in a syringe. And so it's just easier time saving for the pharmacist for the infusion nurse and of course for the patients.

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