ASSESSING THE IMPACT OF ADJUVANT THERAPY ON CURE RATE FOR STAGE-2 BREAST-CARCINOMA

The log-rank test is commonly used to assess therapeutic effect in pro spective, randomised clinical trials. This test is sensitive to differ ences in survival between treatment groups at a specific endpoint, but cannot determine whether such a difference is due to an enhanced cure rate or an enhanced survival time among uncured patients. To investig ate the clinical impact of such limitations, an algorithm was construc ted to simulate clinical, randomised, adjuvant therapy trials in patie nts with a cured fraction of 0.27 and a median survival time for uncur ed patients of 3.4 years. Hypothetical therapies were introduced to in crease rate of cure, increase median survival time, or achieve a combi nation of these effects. For 500 simulated patients recruited over a 5 year period and then followed for three additional years, a 50% enhan cement of median survival time (to 5.1 years) led to a survival increa se detectable at the P = 0.05 level in 780 of 1000 trials, whereas a 5 0% enhancement of cured fraction (to 40.5%) led to a detectable increa se at the same level in only 449 of 1000 trials. These findings sugges t that, in clinical trials of adjuvant therapy for stage 2 breast canc er, the log rank test may be more sensitive to increases in tumour-rel ated survival time than to increases in cured fraction.