CHAARTED: QoL Analysis of Docetaxel + ADT in Metastatic Hormone-Sensitive Prostate Cancer CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3-7, 2016 *CCO is an independent medical education company that provides state-of-the-art medical information to healthcare professionals through conference coverage and other educational programs. ADT, androgen deprivation therapy; QoL, quality of life. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

CHAARTED: Docetaxel + ADT in mHSPC Docetaxel first agent to provide survival benefit in mHSPC Significant toxicity associated with docetaxel QoL is an important factor in understanding full clinical benefit of a therapeutic option CHAARTED trial: ADT + docetaxel in hormone-naive mHSPC Docetaxel + ADT significantly prolonged OS over ADT alone (57.6 vs 44.0 mos; HR: 0.61; P = .0003)[1] Analysis includes pt-reported outcomes (QoL, disease-related and treatment-related symptoms) from CHAARTED trial[2] ADT, androgen deprivation therapy; mHSPC, metastatic hormone-sensitive prostate cancer; QoL, quality of life. 1. Sweeney CJ et al. N Engl J Med. 2015; 373:737-746. 2. Patrick-Miller LJ, et al. ASCO 2016. Abstract 5004. Slide credit: clinicaloptions.com

CHAARTED: Study Design for Pt-Reported Outcomes Randomized phase IIIb trial QoL analysis in ITT population Primary endpoint: overall QoL (FACT-P) Secondary endpoints: disease-related symptoms (BPI), treatment-related symptoms (FACIT-F, FACT-T) Stratified by extent of mets (high vs low); age (≥ 70 vs < 70 yrs); ECOG PS (0-1 vs 2); CAB > 30 days (yes vs no); SRE prevention (yes vs no), prior adjuvant ADT (≤ 12 vs > 12 mos) ADT + Docetaxel 75 mg/m2 Q3W up to 6 cycles (n = 397) ADT alone (n = 393) Metastatic hormone-sensitive prostate cancer with elevated PSA, ECOG PS 0-2, no prior docetaxel (N = 790) Evaluate QoL at baseline, 3, 6, 9, 12 mos ADT, androgen deprivation therapy; BPI, Brief Pain Inventory; ECOG, Eastern Cooperative Oncology Group; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FACT-P, Functional Assessment of Cancer Therapy-Prostate; FACT-T, Functional Assessment of Cancer Therapy-Taxane; ITT, intent to treat; QoL, quality of life; PS, performance status; PSA, prostate-specific antigen; SRE, skeletal-related event; Slide credit: clinicaloptions.com Patrick-Miller LJ, et al. ASCO 2016. Abstract 5004.

CHAARTED: Pt Characteristics Baseline characteristics well balanced between treatment arms Characteristic, % ADT + Docetaxel (n = 397) ADT alone (n = 393) Median age, yrs (range) 64 (36-88) 63 (39-91) White, % 88.9 88.5 ECOG PS 0, % 69.8 69.4 High volume of metastasis, % 66.2 63.6 No prior localized therapy, % 72.8 73.0 Median time from ADT start to randomization, mos (range) 1.2 (0-3.9) 1.3 (0-3.9) ADT, androgen deprivation therapy; ECOG, Eastern Cooperative Oncology Group; PS, performance status. Baseline characteristics not reported Slide credit: clinicaloptions.com Patrick-Miller LJ, et al. ASCO 2016. Abstract 5004.

CHAARTED: Pt-Reported Outcomes Overall QoL with early docetaxel + ADT worse than ADT alone at 3 mos, superior at 12 mos Treatment-associated symptoms show early worsening with docetaxel + ADT vs ADT alone followed by rebound Disease-associated symptoms (pain) similar between arms Emotional well-being, prostate cancer–specific concerns reported better with docetaxel + ADT vs ADT alone throughout treatment QoL Difference Between Docetaxel + ADT and ADT Alone Estimate SE P Value Baseline -1.00 1.28 .43 3 mos -3.09 1.32 .02 6 mos 0.90 1.34 .50 9 mos 0.29 1.37 .84 12 mos 2.85 1.39 .04 ADT, androgen deprivation therapy; QoL, quality of life; SE, standard error. Slide credit: clinicaloptions.com Patrick-Miller LJ, et al. ASCO 2016. Abstract 5004.

CHAARTED: Conclusions From Pt-Reported Outcomes Larger decline of QoL measures (FACT-P, FACT-T, FACIT-F) in first 3 mos of docetaxel + ADT vs ADT alone[1] However, by 12 mos, return to baseline and to significantly higher FACT-P scores with docetaxel + ADT vs ADT alone[1] No long-term negative impact on QoL with docetaxel + ADT[1] Investigators suggest improvement in QoL at 12 mos and prolonged survival with docetaxel + ADT vs ADT alone, indicates a clinically meaningful benefit of early docetaxel with ADT[1,2] ADT, androgen deprivation therapy; FACIT-F, Functional Assessment of Chronic Illness Therapy-Fatigue; FACT-P, Functional Assessment of Cancer Therapy-Prostate; FACT-T, Functional Assessment of Cancer Therapy-Taxane;QoL, quality of life. 1. Patrick-Miller LJ, et al. ASCO 2016. Abstract 5004. 2. Sweeney CJ et al. N Engl J Med. 2015; 373:737-746. Slide credit: clinicaloptions.com

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