Efficacy of trastuzumab emtansine (T-DM1) and lapatinib after dual HER2 inhibition with trastuzumab and pertuzumab in patient with metastatic breast cancer: Retrospective data from a French multicenter real-life cohort

by Fabien Moinard-Butot, Caroline Saint-Martin, Carole Pflumio, Matthieu Carton, William Jacot, Paul-Henri Cottu, Véronique Diéras, Florence Dalenc, Anthony Goncalves, Marc Debled, Anne Patsouris, Marie-Ange Mouret-Reynier, Laurence Vanlemmens, Marianne Leheurteur, George Emile, Jean-Marc Ferrero, Isabelle Desmoulins, Lionel Uwer, Jean-Christophe Eymard, Bianca Cheaib, Coralie Courtinard, Thomas Bachelot, Michaël Chevrot, Thierry Petit 

The Breast: VOLUME 63, P54-60, JUNE 01, 2022

 

Purpose

Trastuzumab-emtansine (T-DM1), as well as lapatinib plus capecitabine were proven effective in two Phase III studies, following first-line trastuzumab plus a taxane. The introduction of dual HER2 blockade by trastuzumab and pertuzumab as first-line has positioned T-DM1 into second-line, and lapatinib plus capecitabine beyond, without formal evaluation of these strategies.

Methods

ESME Data Platform (NCT03275311) included individual data from all patients aged ≥18 years, in whom first-line treatment for metastatic breast cancer (MBC) was initiated between January 1, 2008 and December 31, 2016 in one of the 18 French Comprehensive Cancer Centers. The efficacy of T-DM1 and lapatinib plus capecitabine combination, following double blockade associating trastuzumab and pertuzumab were evaluated in this national real-life database. Eligibility criteria were: female, MBC, HER2+ tumor, first-line taxane-based chemotherapy and dual HER2-blockage by trastuzumab plus pertuzumab. Cohort A received second-line T-DM1, and Cohort B second-line T-DM1 and third or fourth-line lapatinib plus capecitabine.

Results

Cohort A comprised 233 patients, and Cohort B 47 patients. Median progression-free survival (PFS) was 7.1 months in Cohort A and 4.6 months in Cohort B. Median overall survival were 36.7 months and 12.9 months, respectively. PFS was significantly dependent on the preceding treatment line's duration. In cohort A, HER2 expression status was a significant predictive factor of PFS.

Conclusion

First-line trastuzumab plus pertuzumab do not markedly diminish T-DM1's efficacy in second-line. Similarly, sequential treatment with trastuzumab plus pertuzumab then T-DM1 does not noticeably modify the efficacy of lapatinib plus capecitabine.

 

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

 

Trastuzumab emtansine for HER2-positive metastatic breast cancer: Outcomes from a whole-of-population Australian cohort

by Benjamin Daniels, Belinda E. Kiely, Monica Tang, Nehmat Houssami, Sarah J. Lord, Sallie-Anne Pearson 

The Breast: Published: May 07, 2021

Highlights

•Real-world T-DM1 recipients are older than trial participants.

•Real-world T-DM1 recipients have more prior pertuzumab exposure than trial participants.

•Median overall survival was 10 months shorter than that reported from the trial.

Purpose

We aim to describe the treatment patterns and overall survival (OS) outcomes in patients receiving trastuzumab emtansine (T-DM1) for HER2-positive metastatic breast cancer (HER2+MBC) in routine clinical care.

Methods

Retrospective, whole-of-population cohort study of people initiating T-DM1 for HER2+MBC between October 2015 and May 2019 in Australia. We used dispensing claims to estimate time-to-T-DM1 initiation, duration of treatment, and treatments administered prior to and following T-DM1 therapy. We estimated OS from T-DM1 initiation and stratified results based on whether patients received first- or second-line T-DM1 treatment. We benchmarked outcomes to those reported in the pivotal, EMILIA trial.

Results

345 patients initiated T-DM1: 309 as second-line therapy for HER2+MBC and 36 as first-line therapy. 51% of patients had received endocrine therapy and 98% of second-line patients received pertuzumab prior to starting T-DM1. The median age was 57 years (53 in EMILIA); median time-to-T-DM1 initiation from start of HER2-targeted therapy for HER2+MBC was 11.6 months (IQR: 7.9–16.6); median duration of T-DM1 treatment was 6.5 months (3.1–13.5; 7.6 months in EMILIA), and median OS was 19.3 months (7.9–29.5; 29.9 months in EMILIA).

Conclusions

Our findings highlight differences in patient characteristics (older, more previous pertuzumab therapy) and outcomes (shorter OS) from the T-DM1 pivotal trial and provide real-world estimates that can inform patient, clinician and policy, decisions around the use of HER2-targeted therapies in routine clinical care.