239MO - TILs and overall survival (OS) in HER2+ early breast cancer (eBC): 10-year (yr) updated analysis of the ShortHER trial

Background

We already reported the prognostic role of TILs in HER2+ eBC in the ShortHER trial (distant disease-free survival [DDFS], median follow up: 6 yrs). Here, we present the 10-yr updated analysis including DDFS and OS.

Methods

The ShortHER study randomized 1254 HER2+ eBC patients (pts) to 9 weeks vs 1 yr of adjuvant trastuzumab + chemotherapy (CT). TILs were scored on centralized primary tumor (available for 866 cases). At a median follow up of 9.02 yrs (95% CI 9.00-9.04), the total number of events was 107 for DDFS (24 more than the previously published analysis) and 74 for OS.

Results

In multivariable models including relevant variables (treatment arm, age, menopausal status, stage, histologic grade, hormone receptor status) increased TILs were significantly associated not only with improved DDFS (HR 0.972, 95% CI 0.956-0.989 for each 1% TIL increment, p=0.001) but also with better OS (HR 0.977, 95%CI 0.959-0.996 for each 1% TIL increment, p=0.016). Table shows 10-yr DDFS and OS rates according to different TIL cutoffs. We confirmed the significant interaction between treatment arm and TILs (20% cutoff) for DDFS (p=0.014), with low-TIL pts showing a better outcome with long vs short treatment (10-yr DDFS 88.7% vs 81.0%, p=0.006), and high-TIL pts showing the opposite (10-yr DDFS 87.1% vs 92.2% for long vs short, p=0.091). Regarding OS, pts with TILs≥20% had 10-yr OS rate of 89.3% vs 93.1% in long vs short arm (HR short vs long 0.36 95%CI 0.10-1.36, p=0.131). For pts with TILs

Conclusions

This is the first demonstration of an independent prognostic role of TILs in terms of OS for HER2+ eBC pts treated with adjuvant CT and anti-HER2. Our data suggest that pts with TILs≥20% de-escalating trastuzumab duration are not exposed to an excess risk of death. These data further support the inclusion of immune biomarkers into prognostic tools for HER2+ eBC.

Clinical trial identification

NCT00629278.

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

AIFA (FARMS5KR) and AIRC (MFAG-15938).

Disclosure

M.V. Dieci: Financial Interests, Personal, Advisory Board: Novartis, Eli lilly, Seagen, Exact Science, Daiichi Sankyo, Gilead, reveal genomics; Financial Interests, Personal, Other, Consultancy: Pfizer; Financial Interests, Personal, Invited Speaker: Exact sciences, Gilead, Seagen, Daiichi Sankyo, Novartis, Eli lilly; Financial Interests, Personal, Other, Consultancy on educational project: Roche. A. Musolino: Financial Interests, Personal, Advisory Board: Roche, Novartis, Gilead, AstraZeneca; Financial Interests, Institutional, Coordinating PI: Roche; Financial Interests, Institutional, Research Grant: Lilly; Financial Interests, Institutional, Funding: Seagen; Non-Financial Interests, Principal Investigator: Roche, Lilly, Gilead, Novartis. O. Garrone: Financial Interests, Personal, Advisory Board, outside the submitted work: MSD, EISAI, Pfizer; Financial Interests, Personal, Invited Speaker, outside the submitted work: Novartis, Lilly, Daiichi Sankyo, AstraZeneca. A. Ferro: Financial Interests, Personal, Invited Speaker, outside the submitted work: Lilly, Novartis, Pierre-Fabre. F. Miglietta: Financial Interests, Personal, Invited Speaker: Roche, Novartis, Seagen, Pfizer, Lilli; Financial Interests, Personal, Advisory Board: Astrazeneca, MSD; Financial Interests, Personal, Writing Engagement: Menarini. V. Guarneri: Financial Interests, Personal, Invited Speaker: EliLilly, Novartis, GSK, AstraZeneca, Gilead, Exact Sciences; Financial Interests, Personal, Advisory Board: EliLilly, Novartis, MSD, Gilead, EliLilly, merck serono, Exact Sciences, Eisai, Olema Oncology, AstraZeneca, Daiichi Sankyo, Pfizer; Financial Interests, Institutional, Local PI: EliLilly, Roche, BMS, Novartis, AstraZeneca, MSD, Synton Biopharmaceuticals, Merck, GSK, Daiichi Sankyo, Nerviano, Pfizer; Non-Financial Interests, Member: ASCO. All other authors have declared no conflicts of interest.