A drug used to treat advanced breast cancer has had what appears to be unprecedented success in prolonging lives in a clinical trial, researchers reported on Sunday.
Patients who received the drug — Perjeta, from the Swiss drug maker Roche — had a median survival time nearly 16 months longer than those in the control group.
The Swiss drugmaker also has another related drug called Kadcyla, which is also being tested in combination with Perjeta.
Aim
In CLEOPATRA, 808 pts with HER2-positive MBC were randomized to receive 1L placebo (Pla) + T + D or Ptz + T + D. At primary analysis, pertuzumab was shown to increase progression-free survival significantly, with a strong trend to OS benefit. At a second interim analysis (May 2012), OS was improved to a degree which was both statistically significant and clinically meaningful (HR = 0.66, 95% CI 0.52–0.84; P = 0.0008) but the median OS in pts who received Ptz was not reached. Here we report results of a subsequent prespecified OS analysis.
Methods
This OS analysis was planned when ≥385 deaths were reported. The log-rank test, stratified by prior treatment status and geographic region, was used to compare OS between arms, applying the Lan-DeMets α-spending function with an O’Brien-Fleming threshold of p ≤ 0.0456. The Kaplan–Meier approach was used to estimate median OS in both arms; a stratified Cox proportional hazard model was used to estimate HR and 95% CIs. Subgroup analyses of OS were performed for stratification factors and other key baseline characteristics.
Results
Median follow-up time was 50 months (mos) and the statistically significant improvement in OS in favor of Ptz + T + D was maintained (HR = 0.68, 95% CI 0.56–0.84; p = 0.0002). Median OS was 40.8 mos in the Pla arm and 56.5 mos in the Ptz arm, the difference at the medians being 15.7 mos. The OS benefit in predefined subgroups was consistent with previous observations. It is to be noted that following the previous report of OS benefit, cross-over therapy was allowed and 48 pts in the Pla arm crossed over to the Ptz arm. The safety profile of Ptz + T + D in the overall population and in pts who crossed over to the Ptz arm was consistent with the known safety profile of Ptz and the long-term cardiac safety profile was maintained.
Conclusions
1L treatment with Ptz + T + D significantly improved OS for pts with HER2-positive MBC compared with Pla + T + D, providing a 15.7 mo increase in the median values. The 56.5 mo median OS is unprecedented in 1L MBC and this substantial improvement confirms the Ptz regimen as 1L standard of care for pts with HER2-positive MBC.
Sources and Press Releases:
- Pertuzumab Adds 16 Months Survival Benefit to Trastuzumab and Chemotherapy Treatment for HER2-Positive Metastatic Breast Cancer, ESMO 2014 Press Release, 28 Sep 2014.
- Final overall survival (OS) analysis from the CLEOPATRA study of first-line (1L) pertuzumab (Ptz), trastuzumab (T), and docetaxel (D) in patients (pts) with HER2-positive metastatic breast cancer (MBC), ESMO 2014, 28.09.2014.
- Roche Breast Cancer Drug Appears to Greatly Extend Patients’ Lives, NYTimes, SEPT. 28, 2014.
- Roche breast cancer drug shows ‘unprecedented’ survival benefit, Reuters, 28.09.2014.
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