Abstract P4-12-26: A phase II randomized study of lapatinib in combination with capecitabine, vinorelbine or gemcitabine as first or second line-therapy in patients with HER2 positive metastatic breast cancer progressing after taxane (LACOG 0801)
Authors: Gomez H , Neciosup S , Tosello C , Mano M , Bines J , Ismael G , Santi PX , Pinczowsky H , Neron Y , Fanelli M , Fein L , Sampaio C , Lerzo G , Capo A , Zarba JJ , Blajman C , Varela MS , Martínez-Mesa J , Werutsky G , Barrios CH 
Published: August 2014

Abstract
Background:
Lapatinib-Capecitabine (LC) is approved for the treatment of advanced or metastatic breast cancer (MBC) whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane (T), and trastuzumab (H). LACOG 0801 evaluated different L-based chemotherapies as first and second-line treatments in MBC.
Methods:
This is a randomized, open label, multicenter, phase II trial of L 1250 mg BID given continuously in combination with C 2000 mg/m2 d1-14 (LC), or Vinorelbine (V) 25mg/m2 d1 and 8 (LV) or Gemcitabine (G) 1000 mg/m2 d1 and 8 (LG), in 21 days cycles. Primary endpoint was ORR (RECIST). Secondary endpoints included progression free survival (PFS), overall survival, tolerability and safety. Patients with HER2 positive MBC who had failed a T-based treatment and who had ≤1 chemotherapy regimen in the metastatic setting were included. Prior therapy with H was not mandatory. Patients were stratified by the presence of liver metastasis, previous use of H, and T administered in the neo/adjuvant or the metastatic setting. With an expected ORR of 23% in the control arm (LC), we hypothesized an absolute increase of 12% in the experimental arms using Simon's design.
Results:
A total of 142 pts from Argentina, Brazil and Peru were included from 2009-2012. Patient baseline characteristics were well balanced between the three arms. Median age was 51y, 58% postmenopausal, 65% ECOG 1, 49% had visceral disease (32% liver metastasis), 57% hormone receptor negative and only 47% had received prior H. Median number of administered cycles was 6 (LC = 5; LV = 7; LG = 6). ORR was 47.1% (95%CI 38.5; 67.1), 55.6% (95%CI 29.6; 60.0) and 41.3% (95%CI 43.2; 73.0) in LC, LV and LG, respectively. Median PFS was 9.1m (95%CI 6.1; 14.7), 7.0m (95%CI 5.0; 9.9) and 6.8m (95%CI 5.8; 9.9) in LC, LV and LG arms respectively. Survival data will be updated. The proportion of patients with at least one adverse event (AE) was 96% in all arms. Most common all grade AE were diarrhea (76%), hand-foot syndrome (HFS) (45%) and vomiting (39%) in LC; diarrhea (71%), neutropenia (68%) and nausea (43%) in LV; diarrhea (64%), neutropenia (60%), anemia and increased ALT both 44% in LG. The most frequent grade 3 and 4 AEs were HFS (18%), diarrhea (6%) and increased ALT/AST (4%) in LC; neutropenia (36%), diarrhea (9%) and febrile neutropenia (6%) in LV; and neutropenia (47%), ALT/AST elevation (13%) and rash (4%) in LG. Discontinuation due to toxicity occurred in 16%, 7% and 20% of patients in arms LC, LV and LG respectively.
Conclusion:
LV and LG seems to be active combinations in patients with HER2 positive MBC after T failure. The high ORR observed in this study might be explained, among other factors, by the inclusion of patients with less prior treatment exposure. No new safety signals where reported with these two novel Lapatinib/chemotherapy combinations. The different side effect profile may help in selecting the most appropriate regimen for a particular patient.
Sponsor: Latin American Cooperative Oncology Group (LACOG) with support from GlaxoSmithKline.
ClinicalTrials.gov number NCT01050322.
Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P4-12-26.