1. 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.

2. 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] Pujade-Lauraine E, et al. SGO Abstract LBA2. 3. Wilson MK, et al. Ann Oncol 2017;28: Friedlander M, et al. ASCO Abstract Ledermann JA, et al. ASCO Abstract 5518.
Slide credit: clinicaloptions.com

3. 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 Abstract LBA2. 2. Ledermann JA, et al. ASCO Abstract Friedlander M, et al. ASCO Abstract 5507.
Slide credit: clinicaloptions.com

4. 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 Abstract Ledermann JA, et al. ASCO Abstract 5518.

5. 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 Abstract 5518.

6. 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 Abstract 5518.

7. 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: with olaparib vs with placebo (difference: -0.03; 95% CI: 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 Abstract 5507.

8. 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 Abstract 5507.

9. 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
( )
< .0001
Toxicity
3.69
0.71
2.98
( )
.0002
TWiST, time without symptoms of disease or toxicity.
Slide credit: clinicaloptions.com
Friedlander M, et al. ASCO Abstract 5507.

10. 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: with olaparib vs with placebo (difference: -0.03; 95% CI: 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 < 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 Abstract LBA2. 2. Friedlander M, et al. ASCO Abstract Ledermann JA, et al. ASCO Abstract 5518.
Slide credit: clinicaloptions.com

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