Abstract 234P
Background
Previous analyses from P2 and P3 studies showed that PAL + ET prolongs TTC vs placebo (PBO) + ET in the overall population of pts with HR+/HER2– ABC. Here, we evaluated TTC in relevant pt subgroups.
Methods
These post hoc analyses evaluated TTC by subgroup using data from 2 randomized phase 3 studies of women with HR+/HER2– ABC. In P2, postmenopausal pts previously untreated for ABC were randomized 2:1 to receive PAL (125 mg/d, 3/1 schedule) + letrozole (LET; 2.5 mg/d) (n=444) or PBO + LET (n=222). In P3, pre/postmenopausal pts whose disease had progressed after prior ET were randomized 2:1 to receive PAL (125 mg/d, 3/1 schedule) + fulvestrant (FUL; 500 mg) (n=347) or PBO + FUL (n=174).
Results
More patients in the PBO + ET vs PAL + ET group received first subsequent chemotherapy (CT) after discontinuation of study treatment (46.8% vs 33.6% and 74.7% vs 69.7% in P2 and P3, respectively). Across all subgroups analyzed, TTC was longer with PAL + ET vs PBO + ET (Table). Regardless of treatment arm, a higher percentage of pts who received vs who did not receive first subsequent CT were aged <65 years (PAL arm: 71% vs 53% in P2, 80% vs 64% in P3; ET arm: 70% vs 58% in P2, 77% vs 71% in P3) or had a disease-free interval (DFI) of ≤12 months (P2: PAL arm: 32% vs 17%; ET arm: 27% vs 17%). A higher percentage of pts with visceral metastases in the PBO arm received first subsequent CT vs those who did not (60% vs 41% in P2, 65% vs 46% in P3); in contrast, in the PAL arm, similar percentages of pts received vs did not receive first subsequent CT (50% vs 47% in P2, 57% vs 59% in P3). Table: 234P
Median time (mo) to first subsequent chemotherapy
| PALOMA-2 | PALOMA-3 | |||||
| TTC | HR (95% CI) | TTC | HR (95% CI) | |||
| PAL + LET | PBO + LET | PAL + FUL | PBO + FUL | |||
| ITT | 40 | 30 | 0.7 (0.6–0.9) | 18 | 9 | 0.6 (0.5–0.7) |
| Visceral | 34 | 25 | 0.6 (0.5–0.9) | 15 | 6 | 0.6 (0.4–0.8) |
| Nonvisceral | 46 | 35 | 0.9 (0.6–1.2) | 23 | 17 | 0.6 (0.4–0.9) |
| Bone only | 40 | 30 | 0.7 (0.4–1.2) | 23 | 20 | 0.8 (0.5–1.2) |
| Liver involvement | 20 | 14 | 0.7 (0.5–1.1) | 13 | 6 | 0.6 (0.4–0.8) |
| Lung involvement | 47 | 30 | 0.6 (0.4–0.8) | 17 | 8 | 0.6 (0.4–0.8) |
| DFI ≤12 mo | 24 | 17 | 0.8 (0.5–1.2) | – | – | – |
| DFI >12 mo | 46 | 31 | 0.6 (0.5–0.9) | – | – | – |
| Pts without prior CT in ABC | – | – | – | 18 | 12 | 0.6 (0.5–0.8) |
| Pts with prior CT in ABC | – | – | – | 14 | 7 | 0.6 (0.4–0.8) |
CI=confidence interval; HR=hazard ratio; ITT=intent-to-treat population.
Conclusions
Across all subgroups, PAL + ET vs PBO + ET prolonged TTC. As expected, pts in P2 who received PAL + ET in the first-line setting had a longer time to subsequent CT than pts in P3 who received PAL + ET after progressing on prior ET.
Clinical trial identification
NCT01740247; NCT01942135.
Editorial acknowledgement
Editorial support was provided by Anny Wu, PharmD, of ICON plc (North Wales, PA, USA), and was funded by Pfizer Inc.
Legal entity responsible for the study
Pfizer Inc.
Funding
Pfizer Inc.
Disclosure
H.S. Rugo: Financial Interests, Institutional, Research Grant: Pfizer Inc; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Odonate; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Seattle Genetics; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Macrogenics; Financial Interests, Institutional, Research Grant: Sermonix; Financial Interests, Institutional, Research Grant: Boehringer Ingelheim; Financial Interests, Institutional, Research Grant: Polyphor; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Other: PUMA; Financial Interests, Personal, Other: Samsung; Financial Interests, Personal, Other: Mylan; Financial Interests, Institutional, Research Grant: Immunomedics. S. Im: Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Personal, Advisory Role: Hanmi; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Pfizer Inc; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: AstraZeneca. A.A. Joy: Financial Interests, Personal, Advisory Role: Pfizer Inc; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Amgen; Financial Interests, Personal, Advisory Role: Exact Sciences; Financial Interests, Personal, Advisory Role: Puma; Financial Interests, Personal, Advisory Role: Teva. J.M. Walshe: Financial Interests, Personal, Advisory Role: Roche; Financial Interests, Personal, Advisory Role: Genomic Health; Financial Interests, Personal, Advisory Role: Pfizer Inc. S. Loi: Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Roche; Financial Interests, Institutional, Research Grant: Genentech. K. Puyana Theall, S. Kim, X. Huang, E. Bananis: Financial Interests, Personal, Full or part-time Employment: Pfizer Inc; Financial Interests, Personal, Stocks/Shares: Pfizer Inc. R. Mahtani: Financial Interests, Institutional, Research Grant: Agendia; Financial Interests, Institutional, Research Grant: Amgen; Financial Interests, Institutional, Research Grant: AstraZeneca; Financial Interests, Institutional, Research Grant: Biotheranostics; Financial Interests, Institutional, Research Grant: Daiichi; Financial Interests, Institutional, Research Grant: Eisai; Financial Interests, Institutional, Research Grant: Genentech; Financial Interests, Institutional, Research Grant: Immunomedics; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Research Grant: Merck; Financial Interests, Institutional, Research Grant: Novartis; Financial Interests, Institutional, Research Grant: Pfizer; Financial Interests, Institutional, Research Grant: Puma; Financial Interests, Institutional, Research Grant: Sanofi; Financial Interests, Institutional, Research Grant: Seagen. R.S. Finn: Financial Interests, Institutional, Research Grant: Pfizer Inc; Financial Interests, Personal, Advisory Role: Pfizer Inc; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Bayer; Financial Interests, Personal, Advisory Role: Novartis; Financial Interests, Personal, Advisory Role: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Eisai; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Merck; Financial Interests, Personal, Advisory Role: Roche. V. Diéras: Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Eli Lilly; Financial Interests, Personal, Advisory Role: Pfizer Inc; Financial Interests, Personal, Advisory Role: AbbVie; Financial Interests, Personal, Advisory Role: Novartis Pharma KK; Financial Interests, Personal, Advisory Role: Roche-Peru; Financial Interests, Personal, Advisory Role: AstraZeneca; Financial Interests, Personal, Advisory Role: Daiichi Sankyo; Financial Interests, Personal, Advisory Role: MSD; Financial Interests, Personal, Advisory Role: Seattle Genetics; Financial Interests, Personal, Advisory Role: Eisai. All other authors have declared no conflicts of interest.