Abstract P5-11-05: Making a difficult conversation easier: Estimating and explaining scenarios for survival time in patients with HER2 positive, metastatic breast cancer
Authors: Vasista A , Stockler M , West T , Wilcken N , Kiely B 
Published: May 2016

Aim

Advances in the treatment of HER2 positive metastatic breast cancer (MBC) have resulted in significant improvements in survival time. Therefore, when estimating survival time, HER2 positive MBC now needs to be considered as a separate entity to HER2 negative MBC. Using data from trials of HER2 targeted therapies for HER2 positive MBC, we aimed to estimate worst-case, typical, and best-case scenarios for survival time to provide oncologists with a simple method to estimate and explain survival time to their patients in this situation.

Method

We sought randomised trials of HER2 targeted therapies in MBC published from 2001 to 2014. We recorded median progression free survival (PFS), median overall survival (OS), and extracted the following percentiles (represented scenario) from each OS curve: 90th (worst-case), 75th (lower-typical), 25th (upper-typical), and 10th (best-case). We also estimated these scenarios for each OS curve by multiplying its median by four simple multiples: 0.25 (worst-case), 0.5 (lower-typical), 2 (upper-typical), and 3 (best-case). Estimates were deemed accurate if within 0.75 to 1.33 times the actual value.

Results

We reviewed 10 first-line and 5 subsequent-line trials of HER2 targeted therapies: 8 of trastuzumab, 6 of lapatinib, 2 of trastuzumab-emtansine (TDM-1), 1 of pertuzumab and 1 of neratinib. The mean for median PFS was 11.1 months (interquartile range [IQR], 8.1 – 12.9) for first-line trials and 5.6 months (IQR 3.6 -6.6) for subsequent-line trials. The scenarios for overall survival are tabulated. Follow-up was insufficient for the best-case scenario (10th percentile) to be extracted from any curve. Simple multiples of the median OS provided accurate estimates of the worst-case scenario in 75% of OS curves, lower-typical in 100% and upper-typical in 88%. Characteristics associated with a longer median OS in first-line trials were: dual HER2 targeted therapy (adding a second agent increased the median OS by 25 months [95% CI 12-38, p = 0.001), and more recent year of publication (for each 1 year increase in year of publication, median OS increased by 1 month, [95% CI 0.2 to 2, p=0.02]

Table 1: Scenarios for overall survival Mean(IQR) in monthsTreatment Group(n)Worst-caseLower-typicalMedian OSUpper-typicalBest-case1st-line HER2 trials26769.4 (7.7-11.0)18.8 (16.4 - 20.8)34.2 (29.1-38.4)56.2 (47.1-63.3)Not evaluableSubsequent-line HER2 trials21225.7 (4.1-7.3)10.7 (8.6-12.8)19.9 (15.2-24.4)21.7 (20.0-23.0)Not evaluable

Conclusions

The median OS for women starting first-line HER2 targeted therapies for HER2 positive MBC was on average 34 months. For most OS curves, simple multiples of the median provided accurate estimates of the worst-case (one-quarter of the median) and typical (half to double the median) scenarios for survival. Longer follow-up is needed to determine the best-case scenario, which is likely to be greater than triple the median OS. For a woman starting first-line HER2 targeted therapy, survival time could be explained as a worst-case scenario of less than 9 months, typical scenario of 18 months to 4.5 years, and a best-case scenario of 8 years or longer. This framework will help oncologists discuss survival times with their patients.

Citation Format: Vasista A, Stockler M, West T, Wilcken N, Kiely B. Making a difficult conversation easier: Estimating and explaining scenarios for survival time in patients with HER2 positive, metastatic breast cancer. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr P5-11-05.