Frances M Boyle1, Ian E Smith2, Joyce O'Shaughnessy3, Bent Ejlertsen4, Aman U Buzdar5, Pierre Fumoleau6, William Gradishar7, Miguel Martin8, Beverly Moy9, Martine Piccart-Gebhart10, Kathleen I Pritchard11, Deborah Lindquist12, Mayur Amonkar13, Yingjie Huang13, Erica Rappold13, Lisa S Williams13, Jing Wang-Silvanto13, Tomomi Kaneko13, Dianne M Finkelstein9, Paul E Goss9. 1. Mater Hospital, Sydney, Australia. Electronic address: frances.boyle@sydney.edu.au. 2. Royal Marsden Hospital, London, UK. 3. Baylor Sammons Cancer Center, Texas Oncology, US Oncology, Dallas, TX, United States. 4. Rigshospitalet, DBCG Secretariat, Copenhagen, Denmark. 5. UT MD Anderson Cancer Center, Houston, TX, United States. 6. Centre GF Leclerc, Dijon, France. 7. Northwestern University, Chicago, IL, United States. 8. Hospital Universitario Gregorio Marañón, Universidad Complutense, Madrid, Spain. 9. Massachusetts General Hospital, Boston, MA, United States. 10. Institut Jules Bordet, Université Libre de Bruxelles, Brussels, Belgium. 11. Sunnybrook Odette Cancer Centre, University of Toronto, Toronto, Canada. 12. Arizona Oncology, US Oncology, Sedona, AZ, United States. 13. GlaxoSmithKline, Collegeville, PA, United States; GlaxoSmithKline, Uxbridge, UK.
Abstract
BACKGROUND: To evaluate health related quality of life (HRQOL) in TEACH, a phase III randomized placebo controlled trial of 12 months of adjuvant lapatinib in HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in disease-free survival. METHODS: Women on TEACH completed the Short Form 36-item health survey (version2; SF-36v2) at the baseline, six and 12 months after therapy initiation and six monthly thereafter. Mean changes were compared between treatment groups for two summary measures (Physical and Mental Component Summary scores; PCS and MCS) and eight domain measures (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), and in patients discontinuing therapy. A five-point change was deemed a Minimally Clinically Important Difference (MCID). Response analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a regression analysis identified predictors of worsening HRQOL. FINDINGS: 3074 (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary SF-36v2 scores decreased in both arms but did not reach Minimally Clinically Important Difference (MCID) despite significant incidences of diarrhoea and rash in lapatinib treated patients. At six months, women receiving lapatinib had more significant reductions (p < 0.01 versus placebo) in social functioning. Early treatment discontinuations were more frequent on lapatinib (32% versus 18%), and were associated with more substantial decrements of HRQOL in both arms. For those discontinuing primarily due to adverse events, decrements in HRQOL reached MCID in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant predictor of worsening HRQOL (p < 0.05). INTERPRETATION: Despite frequent but usually mild toxicities, adjuvant lapatinib is not associated with clinically significant decreases in overall HRQOL. These placebo-controlled results may also help to inform physicians and patients using lapatinib in metastatic HER2 positive breast cancer. FUNDING: GlaxoSmithKline. The AVON Foundation NY supported PEG, DF and BM and The Friends of the Mater Foundation supported FB.
RCT Entities:
BACKGROUND: To evaluate health related quality of life (HRQOL) in TEACH, a phase III randomized placebo controlled trial of 12 months of adjuvant lapatinib in HER2 positive (HER2+) early breast cancer which demonstrated marginal benefit in disease-free survival. METHODS:Women on TEACH completed the Short Form 36-item health survey (version2; SF-36v2) at the baseline, six and 12 months after therapy initiation and six monthly thereafter. Mean changes were compared between treatment groups for two summary measures (Physical and Mental Component Summary scores; PCS and MCS) and eight domain measures (physical functioning, role physical, bodily pain, general health, vitality, social functioning, role emotional and mental health), and in patients discontinuing therapy. A five-point change was deemed a Minimally Clinically Important Difference (MCID). Response analysis compared the proportion of patients demonstrating a MCID in HRQOL, and a regression analysis identified predictors of worsening HRQOL. FINDINGS: 3074 (97%) subjects completed baseline SF-36v2. During the initial 12 months, summary SF-36v2 scores decreased in both arms but did not reach Minimally Clinically Important Difference (MCID) despite significant incidences of diarrhoea and rash in lapatinib treated patients. At six months, women receiving lapatinib had more significant reductions (p < 0.01 versus placebo) in social functioning. Early treatment discontinuations were more frequent on lapatinib (32% versus 18%), and were associated with more substantial decrements of HRQOL in both arms. For those discontinuing primarily due to adverse events, decrements in HRQOL reached MCID in Mental Summary scores (MCS) only. Lower baseline HRQOL was a significant predictor of worsening HRQOL (p < 0.05). INTERPRETATION: Despite frequent but usually mild toxicities, adjuvant lapatinib is not associated with clinically significant decreases in overall HRQOL. These placebo-controlled results may also help to inform physicians and patients using lapatinib in metastatic HER2 positive breast cancer. FUNDING: GlaxoSmithKline. The AVON Foundation NY supported PEG, DF and BM and The Friends of the Mater Foundation supported FB.
Keywords:
Adjuvant breast cancer; Early breast cancer; HER2 positive; HRQOL; Health related quality of life; Human Epidermal Growth Factor Receptor (HER2); Lapatinib; Placebo; SF-36; Tykerb/Tyverb Evaluation After Chemotherapy (TEACH) trial