Quantifying trade-offs: quality of life and quality-adjusted survival in a randomised trial of chemotherapy in postmenopausal patients with lymph node-negative breast cancer

Abstract

We evaluated quality of life (QL) and quality-adjusted survival in International Breast Cancer Study Group Trial IX, a randomised trial including 1669 eligible patients receiving tamoxifen for 5 years or three prior cycles of cyclophosphamide, methotrexate and 5-fluorouracil (CMF) followed by 57 months tamoxifen. During the time with CMF toxicity (Tox), without symptoms and toxicity (TWiST), and following relapse (Rel), patients scored their QL indicators and a utility indicator for subjective health estimation between 'perfect' and 'worst' health. Scores were averaged within Tox, TWiST and Rel and transformed to utilities. Mean durations for the three transition times were weighted with utilities to obtain mean quality-adjusted TWiST (Q-TWiST). Patients receiving CMF reported significantly worse scores for most QL domains at month 3, but less hot flushes. After completing chemotherapy, there were no differences by treatment groups. Benefits evaluated by Q-TWiST favoured the additional chemotherapy. CMF provided 3 more months of Q-TWiST for patients with ER-negative tumours, but CMF provided no benefit in Q-TWiST for patients with ERpositive tumours. Q-TWiST analysis based on patient ratings is feasible in large-scale cross-cultural clinical trials.

Quality of life and quality-adjusted survival (Q-TWiST) in patients receiving dose-intensive or standard dose chemotherapy for high-risk primary breast cancer

“…During the TOX and the TWiST states, the patient-derived utility values were similar between the two regimens. Although the utilities in the TWiST state were better than during TOX, they were less than 'perfect,' comparable to those in patients with node-negative disease receiving tamoxifen only or three cycles of CMF (Bernhard et al, 2004). In addition to the threat of a malignant disease, menopausal symptoms, fatigue (Ganz et al, 2002;Fan et al, 2005;Nieboer et al, 2005), and cognitive impairment (Phillips and Bernhard, 2003;Falleti et al, 2005;Stewart et al, 2006), and their secondary effects can impact general well-being in the long run.…”

“…Within each health state, we calculated the median SHE score using all available scores averaged within patients; that is, for TOX the first 6 months on SD-CT and months 2 and 3 on DI-EC. These health estimates were converted to quality weights using a power transformation (Bernhard et al, 2004). As a supplemental analysis, SHE scores were averaged separately within those patients reporting any subjective grade 3 or higher toxicity during chemotherapy.…”

“…Patient-reported quality of life (QL) during adjuvant chemotherapy for early breast cancer shows transient adverse effects during therapy, but it improves after cessation of standard therapy (Hurny et al, 1996;Fairclough et al, 1999;de Haes et al, 2003;Bernhard et al, 2004Bernhard et al, , 2007Land et al, 2004;Martin et al, 2005), dose-intensive therapy (Del Mastro et al, 2002), or high dose therapy (Macquart-Moulin et al, 2000;Brandberg et al, 2003;Peppercorn et al, 2005). Overall QL improves substantially over the first 2 years (Hurny et al, 1996).…”

Quality-adjusted survival as an end point in breast cancer trials

“…The net benefit of adjuvant chemotherapy in older women (with node negative disease) was further investigated by performing a Q-TWiST analysis on the IBCSG-9 trial [38]. The actual duration of adjuvant chemotherapy treatment was used to define the time spent in TOX, and uQoL weights were approximated by applying a bias correction to QoL VAS scores collected longitudinally from trial participants.…”

Impact of a 21‐gene RT‐PCR assay on treatment decisions in early‐stage breast cancer

“…18 Women with nodenegative, receptor-positive ESBC were classified as high (RS ! 31), intermediate (RS [18][19][20][21][22][23][24][25][26][27][28][29][30], or low (RS < 18) risk of distant recurrence at 10 years ( Fig. 1).…”