Q-TWiST analysis of lapatinib combined with capecitabine for the treatment of metastatic breast cancer.
The addition of lapatinib (Tykerb/Tyverb) to capecitabine (Xeloda) delays disease progression more effectively than capecitabine monotherapy in women with previously treated HER2+ metastatic breast cancer (MBC). The quality-adjusted time without symptoms of disease or toxicity of treatment (Q-TWiST) method was used to compare treatments. The area under survival curves was partitioned into health states: toxicity (TOX), time without symptoms of disease progression or toxicity (TWiST), and relapse period until death or end of follow-up (REL). Average times spent in each state, weighted by utility, were derived and comparisons of Q-TWiST between groups performed with varying combinations of the utility weights. Utility weights of 0.5 for both TOX and REL, that is, counting 2 days of TOX or REL as 1 day of TWiST, resulted in a 7-week difference in quality-adjusted survival favouring combination therapy (P=0.0013). The Q-TWiST difference is clinically meaningful and was statistically significant across an entire matrix of possible utility weights. Results were robust in sensitivity analyses. An analysis with utilities based on EQ-5D scores was consistent with the above findings. Combination therapy of lapatinib with capecitabine resulted in greater quality-adjusted survival than capecitabine monotherapy in trastuzumab-refractory MBC patients.
Sherrill
B
B
RTI Health Solutions, Research Triangle Park, NC 27709, USA. bsherrill@rti.org
Amonkar
M M
MM
Stein
S
S
Walker
M
M
Geyer
C
C
Cameron
D
D
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D000069287:Capecitabine; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D018450:Disease Progression; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D006801:Humans; D000077341:Lapatinib; D009362:Neoplasm Metastasis; D011799:Quinazolines / Q000008:administration & dosage; D012008:Recurrence; D016019:Survival Analysis
D011799:Quinazolines; D000077341:Lapatinib; D003841:Deoxycytidine; D000069287:Capecitabine; D005472:Fluorouracil