Confirmed tumor response by molecular subtype in patients with metastatic breast cancer: Sub-analysis from a phase 3 clinical study comparing oral paclitaxel and encequidar to IV paclitaxel.

Abstract

1073 Background: Paclitaxel, a foundation treatment in MBC, is hydrophobic and must be formulated for IV administration with Cremophor EL, increasing the risk of infusion reactions and necessitating pre-treatment with corticosteroids and antihistamines. Paclitaxel cannot be administered orally because it is a substrate for P-gp. The oral bioavailability of paclitaxel is improved when administered 1 hour after the highly selective, potent, and minimally absorbed P-gp inhibitor encequidar. As oral paclitaxel is Cremophor-free there is no need for pretreatment for infusion reactions. While targeted therapies have improved outcomes in patients with HER2+ tumors there is still an unmet need for therapies that prolong survival with reduced toxicity across all tumor subtypes. Methods: A phase 3, open-label, randomized, multicenter study in women with histologically- or cytologically-confirmed MBC for whom treatment with IV paclitaxel monotherapy had been recommended by their oncologist randomized 402 patients 2:1 to either oral paclitaxel and encequidar (oPac+E) or IV paclitaxel (IVPac). Oral paclitaxel 205 mg/m2 was administered once daily for 3 consecutive days, weekly. Encequidar 12.9 mg was administered 1 hour before each dose of oral paclitaxel. IV paclitaxel 175 mg/m2 was infused over 3 hours on day 1 of every 3 weeks. Results: In the ITT population oPac+E was superior to IV paclitaxel with a confirmed tumor response rate of 35.8% vs 23.4% for IVPac: a difference of 12.4% (p = 0.0107). A post-hoc subgroup efficacy analysis was conducted based on tumor subtypes, however, the study was not powered to detect statistical differences within these subgroups. Patients in the HR+/HER2- subgroup had a better tumor response to oPac+E (44.8% vs 21.4% IVPac-response rate difference of 23.4%) as did patients in the TNBC (30.5% vs 20.2%-response rate difference of 10.3%) subgroup. Responses were similar (49% vs 47.4% IVPac) in the HER2+ subgroup. Patients with unknown HER2 status receiving oPac+E had a 58.8% response rate vs 14.3% with IVPac (response rate difference of 44.5%). Conclusions: oPac+E is the first oral taxane to demonstrate superiority in radiologically confirmed tumor response rate compared to IVPac in a group of 402 women with metastatic breast cancer. Patients with HR+/HER2-, TNBC, and Unknown subtypes responded considerably better to oPac+E vs IVPac—especially the HR+/HER2- subtype which represented 63% of the patients treated with oPac+E and 55% of the patients treated with IVPac. Clinical trial information: NCT 02594371 .