Benefit of neoadjuvant chemotherapy in patients (pts) with luminal breast cancer (LBC) is limited. Palbociclib combined with endocrine treatment has shown impressive results in advanced LBC. We conducted a randomized parallel phase II study, assessing letrozole + palbociclib (LP) as neoadjuvant treatment in LBC.
Postmenopausal women were eligible if they had a stage II-III ER-positive HER2-negative BC, not candidate for breast conserving surgery (BCS), with either a PAM50 luminal B, or a PAM50 luminal A profile with proven lymph node involvement (N+). A parallel 1:1 randomization proposed 6 courses of 3rd generation chemotherapy (FEC100 x 3 - docetaxel 100 x 3), or 19 weeks (wks) of L 2.5 mg/day plus P 125 mg/day, 3 wks/4. Surgery was performed at wk 20. Primary endpoint was locally assessed Residual Cancer Burden (RCB) rate. Main secondary endpoints included safety, response rate, positive and negative predictive values of PAM50 ROR (risk of recurrence)-defined status, centrally reviewed RCB, and BCS rates. The protocol planned that the trial should be stopped for futility if ≤ 5 local RCB 0-I events (16.7%) were observed in the first 30 pts in the LP arm.
Out of 184 screened pts, 106 women with Stage II-IIIA, PAM50-ascertained LBC were randomized. Pts had T1-2 (73%) or T3 (27%); N + (26.5%); luminal B (89%) tumors. Median ROR score was 68 (22-93). At interim analysis, RCB 0-I was observed in 1 pt in the LP arm and inclusions were stopped. At final analysis, local RCB 0/I/II/III was observed in 3.8%/3.8%/52%/40.4% of pts in the LP arm, and in 5.9%/9.8%/37.3%/47.1% in the chemo arm, respectively. Central and local RCB results were identical. ROR score was not predictive of RCB 0/1. Clinical objective response rates were 74.5% and 76%, and BCS rates 69.2% and 68.6%, in the LP and chemo arms, respectively. Ki67 final median value was significantly lower in the LP arm [3% (range 1-40) vs 8% (2-15), p=.017). Of 19 serious adverse events, 2 occurred in the LP arm and 17 in the chemo arm (p
Neoadjuvant LP led to a slightly lower pCR/RCB 0-I rate than chemo, however clinical response and BCS rates were similar in both arms and LP had a much better safety profile. Extensive analyses are ongoing.
Clinical trial identification
Legal entity responsible for the study
Pfizer - Nanostring
P. Cottu: Consulting Fees (e.g. advisory boards): Pfizer, Roche, Novartis. Travel: Pfizer, Roche, Novartis. F. Duhoux: Consulting Fees (e.g. advisory boards): Pfizer, Roche. Travel: Amgen, Pfizer, Roche, Teva. All other authors have declared no conflicts of interest.