ASCO 2009-RIBBON-1 A NEGATIVE STUDY?

Abstract:

Background: B in combination with weekly paclitaxel or docetaxel (D) as 1st-line therapy for MBC has improved progression-free survival (PFS) compared with the respective taxane alone in two large Phase III trials. This study investigated the addition of B to standard 1st-line chemotherapy regimens for MBC. Methods: Patients were randomized in 2:1 ratio to receive B + chemotherapy or placebo (pl) + chemotherapy. Prior to randomization, investigators chose capecitabine (Cap) (2000 mg/m² x 14d), taxane (T) (nab-paclitaxel [260 mg/m²] or D [75 or 100 mg/m²], q3wk), or anthracycline (Ant)-based chemotherapy (q3wk). B or pl was administered at 15 mg/kg q3wk. Key eligibility criteria included MBC or locally-recurrent disease, no prior cytotoxic treatment, ECOG PS 0 or 1, HER2-negative disease and no CNS metastases. The primary endpoint was investigator-assessed PFS. Secondary endpoints included overall survival (OS), objective response rate (ORR), independent review of PFS, and safety. At progression, all patients were eligible for B with 2nd line chemotherapy. The Cap cohort and the pooled T or Ant (T + Ant) cohort were independently powered and analyzed in parallel using two-sided stratified log-rank test (Cap: 80% power to detect HR=0.75; T + Ant: 90% power to detect HR=0.7). Results: RIBBON-1 enrolled 1237 patients (Cap, 615; T, 307; Ant, 315) from 12/05 to 8/07 in 22 countries with a median follow-up of 15.6 months in the Cap cohort and 19.2 months in the T + Ant cohort. The results are summarized below. OS data are limited with only 33% of events. Safety was consistent with results of prior B trials. Conclusions: The addition of B to Cap, T; or Ant-based chemotherapy regimens used in 1st-line treatment of MBC resulted in statistically-significant improvement in PFS with a safety profile comparable to prior Phase III studies.

	Cap (n=615)		T + Ant (n=622)
	Pl (n=206)	B (n=409)	Pl (n=207)	B (n=415)
PFS, HR (95% CI)	0.688 (0.564, 0.840)		0.644 (0.522, 0.795)
Log-rank p-value	0.0002		<0.0001
Median (months)	5.7	8.6	8.0	9.2
ORR* (%)	38 (23.6)	115 (35.4)	67 (37.9)	177 (51.3)
p-value	0.0097		0.0054
OS, HR ( 95% CI)	0.847 (0.631, 1.138)		1.032 (0.774, 1.376)
Log-rank p-value	0.2706		0.8298
Median (months)	21.2	29.0	23.8	25.2