BACKGROUND: Median PFS was significantly prolonged for a group of HER2+ post-menopausal patients taking lapatinib +letrozole (Lap+Let) as first-line therapy for hormone receptor positive (HR+) MBC compared with patients on Let plus placebo (Let+pla) in a phase III, randomized, double-blind study. Previous reports showed that QOL was generally stable for patients who stayed on study and that the proportion of QOL responders was similar in the treatment arms. Exploratory analyses were performed to examine the extent to which QOL change scores correlate with tumor progression events.
METHODS: Progression was assessed using RECIST criteria and QOL was assessed using the Functional Assessment of Cancer Therapy-Breast (FACT-B). QOL scores from each time point were pooled across treatment arms for patients who progressed or did not progress up to one week after the assessment; withdrawal assessments were analyzed when they occurred. Average change scores at each time point were compared using least squared means from ANCOVAs, adjusted for baseline value. Higher scores represent better QOL. Distribution of QOL responses stratified by whether change from baseline represented minimally important declines, increases or stability were compared using a chi-squared test.
RESULTS: Among 1286 randomized patients, 219 were identified as HER2+. By the Week 12 assessment (+1 week), 72 patients had progressed; another 37 progressed at Week 24; and 21 more at Week 36. Average changes from baseline in FACT-B total scores were statistically and clinically significant between patients who progressed and those who did not at Week 24 (p=0.0001) and Week 36 (p=0.04) but not at Week 12 (Table 1).At Week 12, the distribution of patients by FACT-B response level was similar between patients who progressed and those who did not (p=0.67). Table 2 shows that among patients who continued on study after Week 12, a higher proportion of patients whose tumors progressed had FACT-B declines >7 points from baseline (p<0.0001).
CONCLUSIONS: Results show that tumor progression is associated with clinically meaningful declines in QOL scores in patients with HR+, HER2+ MBC. Hence, the longer PFS for Lap+Let versus Let+pla is expected to translate into a QOL advantage. However, these hypothesis-generating analyses suggest that QOL declines may take more than a few months to evolve.
