Abstract P6-17-30: Changes in patient, tumor, and treatment characteristics over time in first-line trastuzumab plus taxane (paclitaxel/docetaxel) arms in HER2-positive metastatic breast cancer trials

Abstract

Abstract Background: A retrospective analysis showed improved progression-free survival and consistent underestimation of trastuzumab (H) + taxane (T) efficacy assumptions in first-line (1L) human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer (MBC) trials over time (ISCB 2016). We evaluated changes in baseline and treatment characteristics and the safety profile of H+T in 1L HER2-positive MBC trials conducted during 1995–2015. Methods: Trial-level data on patient, tumor, and treatment characteristics and safety profiles in H+T arms of 15 randomized trials were extracted from published data and clinical study reports. Characteristic and safety profile changes over time were explored by weighted regression; relevance was assessed by F-test. Results: Patient and tumor characteristics were generally stable over time. We observed relevant changes in types of adjuvant therapy used. Serious adverse events (SAEs) and study withdrawals due to Aes decreased over time; rates of treatment discontinuation due to Aes increased. No. of trials (patients)Difference in patients with characteristic per 5 years, % (95% CI)P valueBaseline characteristics Median age15 (2895)0.5 (0.1, 0.9)*.28ECOG status 012 (2472)0.2 (-1.1, 1.6).87Hormone receptor-positive11 (2124)1.3 (-1.1, 3.6).61HER2 IHC 3+8 (1657)5.8 (3.0, 8.6).08Visceral disease10 (1970)0.5 (-2.5, 3.6).86Adjuvant therapy Hormonal therapy11 (2194)-10.1 (-12.4, -7.8).002Radiotherapy9 (2010)-4.2 -5.8, -2.6).035HER2-targeted therapy9 (2176)20.2 (13.0, 27.4).026Chemotherapy15 (2893)-7.0 (-9.2, -4.7).008Safety Grade 3+ AE6 (1342)-15.4 (-28.4, -2.5).30SAE7 (1462)-12.6 (-15.4, -9.8).006Study withdrawal due to AE8 (1525)-6.8 (-9.0, -4.5).023Treatment discontinuation due to AE6 (1370)11.5 (6.7, 16.3).075*Years (95% CI). AE, adverse events; CI, confidence interval; ECOG, Eastern Cooperative Oncology Group; IHC, immunohistochemistry; SAE, serious adverse events. Conclusions: In 1L HER2-positive MBC trials, the percentage of patients who received adjuvant chemo-, hormonal, and radio-therapy decreased from 1995 to 2015. These changes in treatment patterns suggest a shift towards a higher percentage of patients with de novo metastatic vs recurrent disease in 1L MBC trials over time. Adjuvant H use increased following approval in 2005 as expected. While SAEs decreased over time, no firm conclusions on safety management can be made. Citation Format: Badovinac Crnjevic T, Restuccia E, Michielin F, Eng-Wong J, Nüesch E. Changes in patient, tumor, and treatment characteristics over time in first-line trastuzumab plus taxane (paclitaxel/docetaxel) arms in HER2-positive metastatic breast cancer trials [abstract]. In: Proceedings of the 2018 San Antonio Breast Cancer Symposium; 2018 Dec 4-8; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2019;79(4 Suppl):Abstract nr P6-17-30.