QOL and Q-TWIST Measures with Lapatinib in HER2-Positive MBC

October 9, 2009
Christin Melton

Quality of life (QOL) is an important consideration for clinicians when treating patients. Treatments that diminish QOL can result in the patient discontinuing therapy or switching to another drug. Either can thwart efforts to control tumor growth. Beth Sherrill, MS, Global Head, Biometrics, RTI Health Solutions, Research Triangle Park in North Carolina, and associates sought to determine the effects on QOL of adding lapatinib (Tykerb) to letrozole (Femara) in women with HER2-positive metastatic breast cancer (MBC).

Quality of life (QOL) is an important consideration for clinicians when treating patients. Treatments that diminish QOL can result in the patient discontinuing therapy or switching to another drug. Either can thwart efforts to control tumor growth. Beth Sherrill, MS, Global Head, Biometrics, RTI Health Solutions, Research Triangle Park in North Carolina, and associates sought to determine the effects on QOL of adding lapatinib (Tykerb) to letrozole (Femara) in women with HER2-positive metastatic breast cancer (MBC).

The intent-to-treat (ITT) population in the phase III trial consisted of 1286 postmenopausal women with treatment-naïve MBC. Patients were randomized to receive lapatinib plus letrozole or letrozole plus placebo. Sherrill’s team prospectively identified a subset of 219 women with HER2-positive tumors, of whom 111 received the combination treatment and 108 received letrozole alone. They compared QOL and quality-adjusted survival (Q-TWIST) between the two groups. The Q-TWIST method (defined as quality-adjusted time without symptoms or toxicities) was used to “examine quality-adjusted survival comparing the trade-off between treatment toxicities and delayed progression,” the authors said.

They used the FACT-B (Functional Assessment of Cancer Therapy-Breast) instrument to measure QOL. Patients completed the questionnaire on day 1 of the trial, every 12 weeks during treatment, and at study withdrawal. FACT-B includes subscales that evaluate “functional, emotional, and physical well being, as well as the breast cancer subscale that addresses specific items related to the woman’s experience of the disease,” Sherrill said. The researchers looked for deviations from baseline in each arm, in the period when a patient may be undergoing adverse events from either treatment or the disease; the period up until disease progression, when not experiencing adverse events; and the relapse period, following progression, when patients are followed until death for overall survival.

At baseline, Sherrill said, patients in both treatment arms had similar scores on each FACT-B subscale and the breast cancer subscale. On all subsequent questionnaires through week 48, scores remained positive, with never greater than a 2.6-point difference between the cohorts. “Our results when analyzing the QOL measures showed that the mean changes from baseline across the two treatment groups were quite stable over time,” Sherrill said. After 48 weeks, the number of patients on treatment dropped sharply, leaving too few to draw meaningful conclusions.

Sherrill noted that 30% to 40% of patients in both groups experienced improved QOL after initiating treatment. “I think this is a positive message, that these patients are faring better with treatment prior to any further progression,” she said. The duration of grade 3 adverse events prior to progression did not differ significantly between the treatment arms. “The take home message here is that the addition of lapatinib to the regimen did not result in a decline in QOL for the patients during their treatment period.”

Patients in the combination group had significantly longer median PFS, which contributed to a more favorable Q-TWIST outcome. PFS was 8.2 months in the lapatinib plus letrozole arm versus 3 months in the letrozole plus placebo group (HR, 0.71; P = .019). Women who received combination therapy had a TWIST period ~9 weeks longer than those taking letrozole alone, though this did not reach statistical significance. Sherrill concluded, “The significantly longer PFS observed in patients taking lapatinib plus letrozole versus letrozole alone was achieved without a detriment to their QOL associated with adverse events. Efficacy and safety results for the ITT population were published earlier this month in the Journal of Clinical Oncology. Abstract No. 212.