SOLO2: Safety, HRQoL With Maintenance Olaparib in Germline BRCA-Mutated Platinum-Sensitive Relapsed Serous Ovarian Cancer CCO Independent Conference Highlights* of the 2017 ASCO Annual Meeting; June 2-6, 2017; Chicago, Illinois *Clinical Care Options (CCO) is an independent medical education organization that provides conference coverage and other unique educational programs for healthcare professionals HRQoL, health-related quality of life. This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

Olaparib vs Placebo in Platinum-Sensitive Relapsed Serous Ovarian Cancer: Background Olaparib: potent, oral PARP inhibitor[1] FDA approved for OC after ≥ 3 lines of chemotherapy In phase III SOLO2 trial, maintenance olaparib tablet formulation achieved significantly improved mPFS in pts with gBRCA1/2m PSR serous OC vs PBO[2] Investigator assessed mPFS: 19.1 vs 5.5 mos (HR: 0.30; P < .0001) 5th Ovarian Cancer Consensus Conference consensus statement recommends that additional endpoints, including predefined pt-reported outcomes, be added to support PFS as primary endpoint for maintenance therapy in recurrent OC[3] Current analysis of SOLO2 reports HRQoL, pt-centered benefits, safety/tolerability[4,5] gBRCA1/2m, germline BRCA1/2 mutated; HRQoL, health-related quality of life; m, median; OC, ovarian cancer; PBO, placebo; PSR, platinum-sensitive relapsed. 1. Olaparib [package insert]. 2017. 2. Pujade-Lauraine E, et al. SGO 2017. Abstract LBA2. 3. Wilson MK, et al. Ann Oncol 2017;28:727-732. 4. Friedlander M, et al. ASCO 2017. Abstract 5507. 5. Ledermann JA, et al. ASCO 2017. Abstract 5518. Slide credit: clinicaloptions.com

SOLO2: Study Design International, randomized, double-blind phase III trial[1] Olaparib 300 mg BID (n = 196*) RECIST assessment Q12W ± 7 days up to 72 wks, then ~ Q24W until PD or unacceptable toxicity Pts with PSR serous OC and germline BRCA1/2 mutation, ≥ 2 prior lines of platinum-based therapy, CR or PR on most recent therapy (N = 295) Placebo (n = 99) *n = 195 received treatment. Primary endpoint: investigator-assessed PFS Key secondary endpoints: safety/tolerability, PFS2, TFST, TSST, OS, HRQoL HRQoL analyses: Primary: change in FACT-O TOI Secondary pt-centered benefits: QAPFS (PFS + EQ-5D-5L); TWiST (mean PFS - mean toxicity) EQ-5D-5L, EuroQol five dimension questionnaire; FACT-O, Functional Assessment of Cancer Therapy-Ovarian; HRQoL, health-related quality of life; OC, ovarian cancer; PD, progressive disease; PSR, platinum-sensitive relapsed; QAPFS, quality-adjusted PFS; RECIST, Response Evaluation Criteria in Solid Tumors; TFST, time to first subsequent therapy or death; TOI, trial outcome index; TSST, time to second subsequent therapy or death; TWiST, time without symptoms of disease or toxicity. 1. Pujade-Lauraine E, et al. SGO 2017. Abstract LBA2. 2. Ledermann JA, et al. ASCO 2017. Abstract 5518. 3. Friedlander M, et al. ASCO 2017. Abstract 5507. Slide credit: clinicaloptions.com

SOLO2: Most Common Nonhematologic AEs Olaparib (n = 195) Placebo (n = 99) All Grades* Grade ≥ 3† Nausea 75.9 2.6 33.3 Fatigue/asthenia 65.6 4.1 39.4 2.0 Vomiting 37.4 19.2 1.0 Diarrhea 32.8 20.2 Dysgeusia 26.7 7.1 Headache 25.1 0.5 13.1 Abdominal pain 24.1 31.3 3.0 Decreased appetite 22.1 11.1 Constipation 20.5 23.2 AE, adverse events; ALT, alanine aminotransferase; AST, aspartate aminotransferase. *Occurring in ≥ 20% of pts. †Occurring in ≥ 2.5% of pts. Elevated ALT in 10 pts (5.1%) in olaparib arm vs 4 pts (4.0%) in placebo arm Elevated AST in 4 pts (2.1%) in olaparib arm vs 4 pts (4.0%) in placebo arm Slide credit: clinicaloptions.com Friedlander M, et al. ASCO 2017. Abstract 5507. Ledermann JA, et al. ASCO 2017. Abstract 5518.

SOLO2: Most Common GI-Related AEs Incidence, Severity, and Outcome of AEs Occurring in > 35% of Pts Nausea Vomiting Olaparib (n = 195) Placebo (n = 99) Pts with AE, % 76 33 37 19 Pts with serious AE, % 1 AE severity, % Grade 1 Grade 2 Grade 3/4 56 17 3 30 5 15 Outcome, % Recovered/resolved Recovering/resolving Not recovered/resolved Unknown 63 2 11 27 6 36 Management, % Supportive treatment Dose interruption Dose reduction Treatment discontinuation 41 9 7 Median duration of first event, mos 1.72 0.43 0.07 Prevalence of grade ≥ 2 nausea and vomiting did not increase over the 24-mo duration of study treatment and follow-up AE, adverse event; GI, gastrointestinal. Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2017. Abstract 5518.

SOLO2: AEs of Fatigue/Asthenia, Anemia Incidence, Severity, and Outcome of AEs Occurring in > 35% of Pts Fatigue/Asthenia Anemia Olaparib (n = 195) Placebo (n = 99) Pts with AE, % 66 39 44 8 Pts with serious AE, % 1 4 AE severity, % Grade 1 Grade 2 Grade 3/4 38 23 22 15 2 12 19 5 Outcome, % Recovered/resolved Recovering/resolving Not recovered/resolved Unknown 34 29 24 13 7 Management, % Supportive treatment Dose interruption Dose reduction Treatment discontinuation 3 17 Median duration of first event, mos 5.78 2.04 2.79 2.60 Prevalence of grade ≥ 2 fatigue/asthenia and anemia did not increase over the 24-mo duration of study treatment and follow-up AE, adverse event. Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2017. Abstract 5518.

SOLO2: HRQoL Analysis High compliance with FACT-O and EQ-5D-5L both on study and during follow-up FACT-O TOI analysis revealed no significant detrimental effects on HRQoL with olaparib vs placebo Pts were relatively well at the start of maintenance therapy Mean TOI: 75 (scale: 0-100; higher score indicates better HRQoL) Olaparib did not have a negative effect on mean TOI score over 12 mos Adjusted mean change in TOI from BL to 12 mos: -2.90 with olaparib vs -2.87 with placebo (difference: -0.03; 95% CI: -2.19 to 2.13; P = .98) BL, baseline; EQ-5D-5L, EuroQol five dimension questionnaire; FACT-O, Functional Assessment of Cancer Therapy-Ovarian; HRQoL, health-related quality of life; TOI, trial outcome index. Slide credit: clinicaloptions.com Friedlander M, et al. ASCO 2017. Abstract 5507.

SOLO2: Quality-Adjusted PFS QAPFS significantly longer with olaparib vs placebo Olaparib (n = 185) Placebo (n = 94) Difference (95% CI) P Value Mean PFS, mos 17.55 8.94 8.61 (6.47 to 10.87) < .0001 Mean utility (mixed model) 0.80 0.81 -0.02 (-0.05 to 0.02) .284 QAPFS, mos 13.96 7.28 6.68 (4.98 to 8.54) QAPFS, quality-adjusted PFS. Slide credit: clinicaloptions.com Friedlander M, et al. ASCO 2017. Abstract 5507.

SOLO2: Time Without Symptoms of Disease or Toxicity TWiST duration significantly longer with olaparib vs placebo Duration, Mos Olaparib (n = 185) Placebo (n = 94) Difference (95% CI) P Value TWiST 13.5 7.21 6.29 (2.95-8.58) < .0001 Toxicity 3.69 0.71 2.98 (1.52-4.68) .0002 TWiST, time without symptoms of disease or toxicity. Slide credit: clinicaloptions.com Friedlander M, et al. ASCO 2017. Abstract 5507.

SOLO2: Conclusions In pts with gBRCA1/2m PSR serous OC, olaparib tablet formulation achieved significantly improved investigator-assessed PFS and secondary endpoints of TFST and TSST[1,2] Safety profile of olaparib tablet formulation consistent with previous observations for capsule formulation[2,3] No significant detrimental effect on HRQoL with olaparib vs placebo Adjusted mean change in FACT-O TOI from BL to 12 mos: -2.90 with olaparib vs -2.87 with placebo (difference: -0.03; 95% CI: -2.19 to 2.13; P = .98) Significant improvement in pt-centered benefits with olaparib vs placebo despite higher olaparib-associated toxicity Significantly longer quality-adjusted PFS and TWiST (P < .0001 for both) BL, baseline; FACT-O, Functional Assessment of Cancer Therapy-Ovarian; gBRCA1/2m, germline BRCA1/2 mutated; HRQoL, health-related quality of life; OC, ovarian cancer; PSR, platinum-sensitive relapsed; TFST, time to first subsequent therapy or death; TOI, trial outcome index: TSST, time to second subsequent therapy or death; TWiST, time without symptoms of disease or toxicity. 1. Pujade-Lauraine E, et al. SGO 2017. Abstract LBA2. 2. Friedlander M, et al. ASCO 2017. Abstract 5507. 3. Ledermann JA, et al. ASCO 2017. Abstract 5518. Slide credit: clinicaloptions.com

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