Abstract CT041: Primary results from FAIRLANE (NCT02301988), a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) + paclitaxel (PAC) for early triple-negative breast cancer (eTNBC)
Authors: Oliveira Mafalda , Saura Cristina , Calvo Isabel , Andersen Jay , Coelho José Luis Passos , Gil Miguel Gil , Bermejo Begoña , Patt Debra A. , Ciruelos Eva , Singel Stina M. , Maslyar Daniel J. , Wongchenko Matthew , Chan Wai Y. , Kapp Amy V. , Peña Lorena de la , Baselga José , Isakoff Steven J. 
Published: August 2018

Abstract
Purpose: This hypothesis-generating trial evaluated neoadjuvant IPAT + PAC for eTNBC.
Methods: Patients (pts) with eTNBC, T ≥1.5 cm and N0-2 were randomized 1:1 to receive 12 wks of weekly PAC 80 mg/m² + either IPAT 400 mg or PBO d1-21 q28d before surgery. Investigators chose adjuvant therapy. Stratification factors were PTEN status (Targos IHC), nodal status and tumor size. Co-primary endpoints were pathologic complete response (pCR) rate (ypT0/TisN0) in the intent-to-treat (ITT) and PTEN-low (Ventana IHC) populations. Secondary endpoints included pCR rate in pts with PIK3CA/AKT1/PTEN-altered tumors (NGS; Foundation Medicine), pre-surgery clinical response rates by MRI and safety.
Results: From Feb 2015 to Mar 2017, 151 pts were randomized. Most had T1/2 (87%) N0 (65%) tumors. At the final analysis (9 Nov 2017), 132 pts (87%) had completed surgery. In all 3 populations, rates of pCR, overall clinical response and complete response (CR) by MRI favored IPAT (Table). IPAT was associated with more grade ≥3 AEs (32% vs 16% with PBO), especially diarrhea (17% vs 1%). AEs leading to IPAT/PBO discontinuation (9% vs 3%) or dose reduction (16% vs 1%) or PAC interruption (20% vs 12%) were more common with IPAT but median PAC dose intensity was 100% (IQR 100-100%) in both arms. Incidences of neuropathy (57% vs 61%) and neutropenia (14% vs 13%) were similar with IPAT vs PBO.
Conclusions: Adding IPAT to PAC for eTNBC showed a small non-significant increase in pCR rate. The anti-tumor effect of IPAT was most pronounced in biomarker-selected pts: CR rates were 32% vs 6% in pts with PTEN-low tumors and 39% vs 9% in PIK3CA/AKT1/PTEN-altered tumors. Safety was consistent with prior IPAT + PAC experience. Similar to LOTUS in metastatic TNBC, FAIRLANE results support further evaluation of IPAT + PAC in pts with PIK3CA/AKT1/PTEN-altered tumors. A comprehensive translational research program is ongoing.
TableEndpointITTPTEN-low (by IHC)PIK3CA/AKT1/PTEN-altered (by NGS)IPAT + PACPBO + PACIPAT + PACPBO + PACIPAT + PACPBO + PACpCR rate (ypT0/TisN0)13/76 (17.1%)10/75 (13.3%)3/19 (15.8%)2/16 (12.5%)5/28 (17.9%)4/34 (11.8%)Difference (95% CI)3.8% (-9.0 to 16.5)3.3% (-25.5 to 32.1)6.1% (-15.0 to 27.2)Overall clinical response ratea by MRI51/76 (67.1%)42/75 (56.0%)14/19 (73.7%)8/16 (50.0%)19/28 (67.9%)18/34 (52.9%)Difference (95% CI)11.1% (-5.6 to 27.9)23.7% (-13.6 to 60.9)14.9% (-12.4% to 42.3%)CR rateb by MRI21/76 (27.6%)10/75 (13.3%)6/19 (31.6%)1/16 (6.3%)11/28 (39.3%)3/34 (8.8%)aUnconfirmed complete or partial response. bUnconfirmed complete response.
Citation Format: Mafalda Oliveira, Cristina Saura, Isabel Calvo, Jay Andersen, José Luis Passos Coelho, Miguel Gil Gil, Begoña Bermejo, Debra A. Patt, Eva Ciruelos, Stina M. Singel, Daniel J. Maslyar, Matthew Wongchenko, Wai Y. Chan, Amy V. Kapp, Lorena de la Peña, José Baselga, Steven J. Isakoff. Primary results from FAIRLANE (NCT02301988), a double-blind placebo (PBO)-controlled randomized phase II trial of neoadjuvant ipatasertib (IPAT) + paclitaxel (PAC) for early triple-negative breast cancer (eTNBC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr CT041.