Octreotide LAR and tamoxifen versus tamoxifen in phase III randomize early breast cancer trials: NCIC CTG MA.14 and NSABP B-29
Judith-Anne W Chapman, Joseph P Costantino, Bin Dong, Richard G Margolese, Kathleen I Pritchard, Lois E Shepherd, Karen A Gelmon, Norman Wolmark, Michael N Pollak, Judith-Anne W Chapman, Joseph P Costantino, Bin Dong, Richard G Margolese, Kathleen I Pritchard, Lois E Shepherd, Karen A Gelmon, Norman Wolmark, Michael N Pollak
Abstract
NCIC CTG MA.14 and NSABP B-29 trials examined the addition of Octreotide LAR (OCT) to 5 years of tamoxifen (TAM). Gallbladder toxicity led to B-29 discontinuation of OCT, and MA.14 OCT administration shortened to 2 years. Median follow-up was 9.8 years for 667 MA.14 patients and 6.8 years for 893 B-29 patients. The primary endpoint was disease-free survival (DFS), defined as time from randomization to time of breast cancer recurrence; second primary cancer other than squamous or basal cell skin carcinoma, cervical carcinoma in situ, or lobular breast carcinoma in situ; or death. The primary statistical test was a univariable pooled stratified log-rank test; multivariable assessment was with Cox regression. For MA.14, 97% of patients were ≥50 years; for B-29, 62%. MA.14 patients were 53% lymph node negative (LN-) while B-29 were 100% LN-; 33% of MA.14 patients received adjuvant chemotherapy, 2% concurrently, while B-29 had 53% concurrent chemotherapy. MA.14 patients were 90% hormone receptor positive; B-29, 100%. MA.14 patients experienced 5-year DFS of 80% with TAM, 76% with TAM + OCT; B-29 patients had 5-year DFS of 88% for both arms. Pooled univariable TAM + OCT to TAM hazard ratio (HR) was 0.99 (95% CI 0.81-1.20; p = 0.69): for MA.14, HR = 0.94 (0.73-1.20; p = 0.50); for B-29, HR = 1.09 (0.80-1.50; p = 0.59). Multivariable pooled HR = 0.98 (0.81-1.20; p = 0.84). Older patients (p < 0.001), with higher T stage (p < 0.001), and LN + (p < 0.001) had shorter DFS. Addition of OCT to TAM did not significantly improve DFS; gallbladder toxicity shortened the additional administration of OCT. This does not negate targeting the insulin-IGF-I receptor family with less toxic therapeutics.
Trial registration: ClinicalTrials.gov NCT00002864 NCT00002967.
Conflict of interest statement
Conflict of interest Dr. Kathleen I Pritchard has declared conflict of interest with AstraZeneca, Pfizer, Roche, Amgen, Novartis, GlaxoSmithKline, and Eisai. Dr. Karen A. Gelmon has declared conflict of interest with Novartis, AstraZeneca, Pfizer, and Roche. No other authors have declared any conflict of interest.
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Source: PubMed