Optimal Survival May Depend on Timing of Paclitaxel, Study Says

There are more than 50 drug regimens available to treat metastatic breast cancer but little guidance on the best order to deliver them, according to a study published in JCO Clinical Cancer Informatics.

Treatment timing may affect overall survival in women with estrogen receptor (ER)—positive, human epidermal growth factor receptor 2 (HER2)–negative metastatic breast cancer (mBC), according to study results published in JCO Clinical Cancer Informatics.

There are more than 50 drug regimens available to treat mBC, but little guidance from the National Comprehensive Cancer Network on the best order to deliver them to achieve optimal results, noted the study authors, who investigated the interrelationship of prior treatment time, previous lines of therapy, and survival following treatment with paclitaxel.

Their retrospective cohort study incorporated data from Flatiron Health on 234 women with ER—positive, HER2-negative mBC with distant metastasis in 2014, chosen to ensure consistent guideline-based treatment options and 5-year follow-up, and a primary cancer diagnosis that occurred after 1980. The primary outcome of overall survival (OS) was defined as, “time from initiation of drug of interest in the metastatic setting to death as a result of any cause.”

The median (interquartile range [IQR]) age at primary diagnosis was 57 (IQR, 48-66) years, 69% of the women were white, and 63% had recurrent mBC. They were followed for a maximum of 70 months. Treatment duration lasted from the first date therapy was administered to death or 30 days after their final treatment, while progression-free survival (PFS) was based on the first date of therapy through date of disease progression.

There were several important findings. The median survival was 20 (IQR, 8-53) months, and there was a negative correlation between OS and when paclitaxel was administered in the course of treatment. There was a 16% greater hazard of death (HR, 1.16; 95% CI, 1.05-1.29) following receipt of paclitaxel for every year on treatment before receiving the taxane therapy.

This increased hazard of death remained elevated through several measures of prior treatments:

  1. 1 prior treatment: HR, 1.71 (95% CI, 1.03-2.84)
  2. 2 prior treatments: HR, 1.30 (95% CI, 0.77-2.21)
  3. At least 3 prior treatments: HR, 2.23 (95% CI, 1.42-3.53)

In addition, results show increased HRs for patients who had metastatic disease diagnosed in both 2013 and 2015:

  • 2013: HR, 1.12 (95% CI, 1.03-1.22)
  • 2015: HR, 1.30 (95% CI, 1.16-1.47)

In addition, the patients shown to have longer survivals after their initial diagnosis, “had prolonged duration of endocrine therapy prior to paclitaxel and other chemotherapies.”

“Prior time on treatment should be considered as a stratifying factor in randomized trials and a confounding factor when examining survival in observational data,” concluded the authors. “This visualization approach can enhance our capacity to harness the power of patient-level data to better understand treatment patterns and their influence on survival outcomes.”

To make progress in optimizing sequential treatment for patients with cancer, they suggest adjustments to data analyzation in future studies: randomizing study participants by time on previous treatment and accounting for confounding by prior treatment duration.

Also, because more than 90% of trials among patients with ER-positive, HER2-negative mBC do not produce meaningful improvements in OS and PFS, the authors are calling for future studies to address the effects of pre- and posttrial treatments on these patients.


Rocque GB, Gilbert A, Williams CP, et al. Prior treatment time affects survival outcomes in metastatic breast cancer. JCO Clin Cancer Inform. 2020;4:500-513. doi:10.1200/CCI.20.00008