Introduction
Treatment intensification with adjuvant CDK4/6 inhibitors has improved disease-free survival, in monarchE and NATALEE trials with abemaciclib and ribociclib respectively, using different eligibility criteria. We assessed the proportion of breast cancer patients represented with these criteria, and their outcome, in an Australian population.
Methods
Consecutive patients from ACT Breast Cancer Treatment Group (6/1997 – 6/2017) were analysed. Patients eligible for monarchE had >=4+ lymph nodes (LN) or 1-3+ LN plus tumour >=5cm or grade 3. NATALEE additionally included LN-negative >5cm, and 2.1–5cm grade 3 cancers. Groups were compared by Chi-square testing; survival estimated by Kaplan-Meier method.
Results
Of 3840 hormone receptor-positive HER2-negative breast cancer patients, 718 (18.7%) qualified monarchE criteria; 2024 (52.7%) were NATALEE-eligible. monarchE-eligible patients were younger (median 56 versus 59 years, p<0.001), with higher proportion premenopausal (34% versus 22%, p<0.001). Significantly more monarchE-eligible patients received chemotherapy (81% versus 33%, p<0.001). Median overall survival was shorter for monarchE-eligible patients (61 versus 105 months, HR 1.89, 95%CI 1.60 – 2.22, p<0.001).
NATALEE-eligible patients were more likely premenopausal with higher chemotherapy-use (66% versus 16%) than non-eligible patients. Node-negative patients comprised 31% of the NATALEE-eligible cohort, while 26% of LN-negative patients qualified for NATALEE. Survival among NATALEE-eligible patients was inferior to non-eligible patients, median 78 versus 106 months (HR 1.36, 95%CI 1.16 – 1.59, p<0.001).
Among NATALEE-eligible patients, 65% (n=1306), or 34% of study population, did not qualify for monarchE. Patients eligible for both study criteria had inferior survival to NATALEE-eligible-only patients (median 61 vs 96 months, HR 1.78, 95%CI 1.47 – 2.14, p<0.001).
Conclusions
Both trial criteria effectively identified high-risk patients for treatment escalation. monarchE selected the highest risk subgroup with the poorest survival. NATALEE identified an additional 34% of hormone receptor-positive breast cancer patients (26% of LN-negative population) eligible for adjuvant CDK4/6 inhibitor therapy, although absolute benefits maybe smaller given lower baseline risk compared with the monarchE population.