Abstract 161P
Background
To estimate the long-term consequences of disease recurrence following treatment with adjuvant T-DM1 in U.S. patients with high-risk HER2+ ESBC who did not achieve pathologic complete response (pCR) after neoadjuvant therapy.
Methods
A Markov model was used to simulate local/regional and distant recurrence with 10 years of follow-up. This corresponds to the estimated number of U.S. patients with incident high-risk HER2+ ESBC in 2021 (n=10,000), which was derived from SEER population-based estimates, the NEOSPHERE trial and expert clinical opinion. The probability of recurrence was based on the T-DM1 arm in the KATHERINE trial and long-term results from the HERA trial. We assumed that 80% of patients with any recurrence experience distant recurrence, while the remainder have local/regional recurrence. SEER data and literature review were used to estimate probabilities of survival and distant recurrence secondary to local/regional recurrence. Model outcomes included: recurrences, breast cancer-related deaths and non-breast cancer-related deaths. Results were compared to a scenario in which there was no recurrence to estimate population impact. All outcomes were also projected over 10 annual incident cohorts, each with 10 years of follow-up.
Results
We estimated the 2021 U.S. patient cohort would experience 2,279 recurrences, including 1,834 distant and 1,559 breast cancer-related deaths over 10 years, resulting in 7,744 lost years of life. Projection to 10 years of incident cohorts would lead to approximately 23,000 recurrences, 16,000 deaths and 77,000 lost years of life. Table: 161P
Findings for 2021 cohort projected over 10 years
| With recurrence | No recurrence | Difference | |
| Local/regional recurrencesDistant recurrences | 4451,834 | 00 | 4451,834 |
| Breast cancer deathsNon-breast cancer deaths | 1,559416 | 0457 | 1,559–41 |
| Life years | 90,249 | 97,993 | –7,744 |
Conclusions
Patients with HER2+ ESBC who do not achieve pCR after neoadjuvant therapy are at ongoing risk of recurrence despite the effectiveness of treatment with T-DM1. There is substantial clinical value in further reducing the recurrence risk among this population.
Clinical trial identification
Editorial acknowledgement
Lee Miller, Miller Medical Communications.
Legal entity responsible for the study
Puma Biotechnology Inc.
Funding
Puma Biotechnology Inc.
Disclosure
D.L. Veenstra: Financial Interests, Personal, Advisory Role: Puma Biotechnology Inc.; Financial Interests, Personal, Advisory Role: Genentech; Financial Interests, Personal, Advisory Role: Mirati Therapeutics; Financial Interests, Personal, Advisory Role: Halozyme Therapeutics; Financial Interests, Institutional, Research Grant: Foundation Medicine. N. Hendrix: Financial Interests, Personal, Stocks/Shares: ALX Oncology; Financial Interests, Personal, Stocks/Shares: Bellicum Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Beyond Air; Financial Interests, Personal, Stocks/Shares: Chimerix; Financial Interests, Personal, Stocks/Shares: Eiger BioPharmaceuticals; Financial Interests, Personal, Stocks/Shares: Myovant Sciences; Financial Interests, Personal, Stocks/Shares: Oncternal Therapeutics; Financial Interests, Personal, Stocks/Shares: Sangamo Therapeutics; Financial Interests, Personal, Stocks/Shares: TRACON Pharmaceuticals; Financial Interests, Personal, Stocks/Shares: Trillium Therapeutics; Financial Interests, Personal, Advisory Role: Halozyme Therapeutics. C.M. Dolan: Financial Interests, Personal, Leadership Role: CMD Consulting Inc.; Financial Interests, Personal, Full or part-time Employment: CMD Consulting Inc.; Financial Interests, Personal, Stocks/Shares: CMD Consulting Inc.; Financial Interests, Personal, Stocks/Shares: Abbott Labs; Financial Interests, Personal, Stocks/Shares: Pfizer; Financial Interests, Personal, Stocks/Shares: Merck; Financial Interests, Personal, Stocks/Shares: Bristol Myers Squibb; Financial Interests, Personal, Advisory Role: Puma Biotechnology Inc.; Financial Interests, Personal, Advisory Role: Myokardia Inc.; Financial Interests, Personal, Advisory Role: REGENXBIO Inc.; Financial Interests, Personal, Advisory Role: Genentech (Roche); Financial Interests, Personal, Advisory Role: Coagulant Therapeutics. K.A. Fisher: Financial Interests, Personal, Full or part-time Employment: CMD Consulting Inc.; Financial Interests, Personal, Advisory Role: Puma Biotechnology Inc.; Financial Interests, Personal, Advisory Role: Myokardia Inc.; Financial Interests, Personal, Advisory Role: REGENXBIO Inc.; Financial Interests, Personal, Advisory Role: F. Hoffmann-La Roche Ltd.; Financial Interests, Personal, Advisory Role: Coagulant Therapeutics. D. Lalla: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology Inc. N. Oestreicher: Financial Interests, Personal, Full or part-time Employment: Puma Biotechnology Inc.; Financial Interests, Personal, Stocks/Shares: Puma Biotechnology Inc. B. Moy: Financial Interests, Institutional, Research Grant: Puma Biotechnology Inc.