PURPOSE: The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation. METHODS: Postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to anastrozole or tamoxifen for 5 years. The primary outcome for this analysis was time to treatment discontinuation. AEs were collected every 6 months post-random assignment from all 3,104 participants and summarized using the Toxicity Index (TI). PRO data were collected at baseline and every 6 months from 1,194 participants. Univariate and multivariable analyses of time to treatment discontinuation were performed using Cox regression models with TIs and PROs as time-dependent covariates. RESULTS: Of 3,046 analyzed participants, 869 (28.5%) discontinued treatment prematurely. In multivariable analysis, when both baseline PROs and on-treatment AEs were considered, thrombosis and arthralgia AEs were associated with discontinuation of both tamoxifen and anastrozole; additional AEs associated with discontinuation varied by drug. In addition, baseline pain interference, hot flashes, and unhappiness were associated with tamoxifen discontinuation (n = 589; overall Harrell's C-statistic 0.686 [95% CI, 0.640 to 0.732]); no baseline PROs were associated with anastrozole discontinuation (n = 589; overall Harrell's C-statistic 0.656 [95% CI, 0.630 to 0.681]). When only baseline PROs were examined, pain interference, hot flashes, and unhappiness were associated with shorter time to discontinuation of tamoxifen; only hot flashes were associated with discontinuation of anastrozole. CONCLUSION: Analysis of AEs using the TI yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of PRO baseline and treatment-emergent symptoms.
PURPOSE: The US National Cancer Institute Moonshot initiative calls for improving analysis and reporting of toxicity to inform treatment tolerability. We used existing clinician-reported adverse event (AE) and patient-reported outcome (PRO) questionnaire data from the randomized, double-blind NSABP B-35 clinical trial to explore reasons for anastrozole and tamoxifen discontinuation. METHODS: Postmenopausal women with ductal carcinoma in situ treated with breast-conserving therapy were randomly assigned to anastrozole or tamoxifen for 5 years. The primary outcome for this analysis was time to treatment discontinuation. AEs were collected every 6 months post-random assignment from all 3,104 participants and summarized using the Toxicity Index (TI). PRO data were collected at baseline and every 6 months from 1,194 participants. Univariate and multivariable analyses of time to treatment discontinuation were performed using Cox regression models with TIs and PROs as time-dependent covariates. RESULTS: Of 3,046 analyzed participants, 869 (28.5%) discontinued treatment prematurely. In multivariable analysis, when both baseline PROs and on-treatment AEs were considered, thrombosis and arthralgia AEs were associated with discontinuation of both tamoxifen and anastrozole; additional AEs associated with discontinuation varied by drug. In addition, baseline pain interference, hot flashes, and unhappiness were associated with tamoxifen discontinuation (n = 589; overall Harrell's C-statistic 0.686 [95% CI, 0.640 to 0.732]); no baseline PROs were associated with anastrozole discontinuation (n = 589; overall Harrell's C-statistic 0.656 [95% CI, 0.630 to 0.681]). When only baseline PROs were examined, pain interference, hot flashes, and unhappiness were associated with shorter time to discontinuation of tamoxifen; only hot flashes were associated with discontinuation of anastrozole. CONCLUSION: Analysis of AEs using the TI yielded important insights into reasons for discontinuation of endocrine therapy that was enhanced by the addition of PRO baseline and treatment-emergent symptoms.
Authors: Kala Visvanathan; Carol J Fabian; Elissa Bantug; Abenaa M Brewster; Nancy E Davidson; Andrea DeCensi; Justin D Floyd; Judy E Garber; Erin W Hofstatter; Seema A Khan; Maria C Katapodi; Sandhya Pruthi; Rachal Raab; Carolyn D Runowicz; Mark R Somerfield Journal: J Clin Oncol Date: 2019-09-03 Impact factor: 44.544
Authors: Richard G Margolese; Reena S Cecchini; Thomas B Julian; Patricia A Ganz; Joseph P Costantino; Laura A Vallow; Kathy S Albain; Patrick W Whitworth; Mary E Cianfrocca; Adam M Brufsky; Howard M Gross; Gamini S Soori; Judith O Hopkins; Louis Fehrenbacher; Keren Sturtz; Timothy F Wozniak; Thomas E Seay; Eleftherios P Mamounas; Norman Wolmark Journal: Lancet Date: 2015-12-11 Impact factor: 79.321
Authors: Harold J Burstein; Christina Lacchetti; Holly Anderson; Thomas A Buchholz; Nancy E Davidson; Karen A Gelmon; Sharon H Giordano; Clifford A Hudis; Alexander J Solky; Vered Stearns; Eric P Winer; Jennifer J Griggs Journal: J Clin Oncol Date: 2018-11-19 Impact factor: 44.544
Authors: Ivana Sestak; Jack Cuzick; Francisco Sapunar; Richard Eastell; John F Forbes; Angelo R Bianco; Aman U Buzdar Journal: Lancet Oncol Date: 2008-08-12 Impact factor: 41.316
Authors: Jacquie H Chirgwin; Anita Giobbie-Hurder; Alan S Coates; Karen N Price; Bent Ejlertsen; Marc Debled; Richard D Gelber; Aron Goldhirsch; Ian Smith; Manuela Rabaglio; John F Forbes; Patrick Neven; István Láng; Marco Colleoni; Beat Thürlimann Journal: J Clin Oncol Date: 2016-05-23 Impact factor: 44.544
Authors: Zahra S Razaee; Arash A Amini; Márcio A Diniz; Mourad Tighiouart; Greg Yothers; André Rogatko Journal: Stat Med Date: 2020-12-20 Impact factor: 2.373
Authors: Vinicius F Calsavara; Márcio A Diniz; Mourad Tighiouart; Patricia A Ganz; N Lynn Henry; Ron D Hays; Greg Yothers; André Rogatko Journal: Qual Life Res Date: 2022-10-17 Impact factor: 3.440