1. OlympiAD: PARP Inhibitor Olaparib Monotherapy in HER2-Negative, BRCA-Mutated MBC
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
gBRCA, germline BRCA; MBC, metastatic breast cancer.
This activity is supported by educational grants from AbbVie, Amgen, AstraZeneca, Celgene Corporation, Genentech, Halozyme, Incyte, and Merck & Co., Inc.

2. OlympiAD: Background
PARP inhibition ceases DNA replication progression and leads to increased double strand DNA breaks, which is typically resolved through homologous recombination[1]
BRCA1 and BRCA2 help facilitate orderly homologous recombination and tumor cells with germline BRCA1/2 mutations are sensitive to PARP inhibition
Olaparib: oral PARP inhibitor with activity in locally advanced and MBC with gBRCA mutations[2,3]
Currently approved for gBRCA-mutated advanced ovarian cancer after ≥ 3 lines of chemotherapy
OlympiAD compared benefit and safety of olaparib monotherapy vs SoC CT in pts with HER2-negative, gBRCA-mutant MBC[4,5]
CT, chemotherapy; gBRCA, germline BRCA; MBC, metastatic breast cancer; SoC, standard of care.
1. Lord CJ, et al. Science. 2017;355: Kaufman B, et al. J Clin Oncol. 2015;33: Tutt A, et al. Lancet. 2010;376: Robson ME, et al. ASCO Abstract LBA4.
Slide credit: clinicaloptions.com

3. OlympiAD: Study Design
Randomized, open-label phase III study
Stratified by HR status (ER+ and/or PgR+ vs TNBC), prior CT for metastases (yes vs no), prior platinum tx (yes vs no)
Pts with HER2-negative MBC with deleterious or suspected deleterious gBRCA mutation; previous anthracycline and taxane, ≤ 2 previous lines of CT* for metastatic disease; if HR+, not suitable for ET or progressed on ≥ 1 ET
(N = 302)
Olaparib 300 mg PO BID
(n = 205)
Until PD or unacceptable AEs
CT† on 28-d cycles
(n = 97)
*If platinum-based therapy, pt could not have experienced progression on tx in advanced setting or ≥ 12 mos since (neo)adjuvant tx.
†Physician’s choice of: capecitabine 2500 mg/m2 PO Days 1-14; vinorelbine 30 mg/m2 IV Days 1, 8; or eribulin 1.4 mg/m2 IV Days 1, 8.
AE, adverse event; BICR, blinded independent central review; CT, chemotherapy; ET, endocrine therapy; gBRCAm, germline BRCA mutation; HRQoL, health-related quality of life; MBC, metastatic breast cancer; PD, progressive disease; RECIST, Response Evaluation Criteria in Solid Tumors; TNBC, triple-negative breast cancer; tx, treatment.
Primary endpoint: PFS per RECIST 1.1 (BICR)
Secondary endpoints: time to second progression/death, OS, ORR, safety, tolerability, global HRQoL
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4. Robson ME, et al. N Engl J Med. 2017;[Epub ahead of print].

4. OlympiAD: Baseline Characteristics
Characteristic, n (%)
Olaparib
(n = 205) CT
(n = 97)
Median age, yrs (range)
44 (22-76)
45 (24-68)
Male
5 (2)
2 (2)
White race
134 (65)
63 (65)
BRCA mutation status
BRCA1
BRCA2
Both
117 (57)
84 (41)
4 (2)
51 (53)
46 (47)
HR status
ER+ and/or PgR+
TNBC
103 (50)
102 (50)
49 (51)
48 (49)
Previous CT for metastasis
146 (71)
69 (71)
Previous platinum tx
60 (29)
26 (27)
Characteristic, n (%)
Olaparib
(n = 205) CT
(n = 97)
De novo MBC
26 (13)
12 (12)
Measurable disease
≥ 2 sites
Bone metastases only
167 (82)
159 (78)
16 (8)
66 (68)
72 (74)
6 (6)
No. CT lines for MBC 1 2
66 (33)
80 (39)
57 (28)
31 (32)
42 (43)
24 (25)
Physician choice CT
Capecitabine
Eribulin
Vinorelbine
N/A
41 (45)
34 (37)
16 (18)
CT, chemotherapy; MBC, metastatic breast cancer; N/A, not applicable; TNBC, triple-negative breast cancer; tx, treatment.
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4.

5. OlympiAD: PFS by BICR (Primary Endpoint)
100 90
Olaparib CT 80
Progression/deaths, n (%) Median PFS, mos
163 (79.5) 7.0
71 (73.2) 4.2 70 60
HR: 0.58 (95% CI: ;
P = .0009)
PFS (%) 50 40 30 20 10
BICR, blinded independent central review; CT, chemotherapy. 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos
Pts at Risk, n
Olaparib CT
205 97
177 63
154 44
107 25
94 21
69 11
40 8
23 4
21 4
11 1
4 1
3 1
2 1
1 0
0 0
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4. Reproduced with permission.

6. OlympiAD: PFS2 by Investigator Assessment
100 90
Olaparib CT 80
Second progression/deaths, n (%) Median PFS2, mos
104 (50.7) 13.2
53 (54.6) 9.3 70 60
HR: 0.57 (95% CI: ;
P = .0033)
PFS2 (%) 50 40 30 20 10
CT, chemotherapy. 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos
Pts at Risk, n
Olaparib CT
205 97
199 85
185 69
152 51
123 42
102 31
75 19
44 10
34 7
18 4
8 1
6 1
5 1
2 0
0 0
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4. Reproduced with permission.

7. OlympiAD: OS by Investigator Assessment
100 90
Olaparib CT 80
Deaths, n (%) Median OS, mos
94 (45.9) 19.3
46 (47.4) 19.6 70 60
HR: 0.90 (95% CI: ;
P = .5665)
OS (%) 50 40 30 20 10
CT, chemotherapy.
OS data at 46% maturity. 2 4 6 8 10 12 14 16 18 20 22 24 26 28
Mos
Pts at Risk, n
Olaparib CT
205 97
205 92
199 85
189 79
178 74
159 69
146 62
109 50
78 34
46 24
30 13
18 9
14 7
8 4
4 2
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4. Reproduced with permission.

8. OlympiAD: Secondary Efficacy Endpoints
Longer time to deterioration (≥ 10 point decrease from BL) with olaparib vs CT for global HRQoL
Median: not reached vs mos
HR: 0.44 (95% CI: ; P = .0043)
PFS Subgroup
HR (95% CI)
P Value
Overall
0.58 ( )
.0009
Prior CT
No prior CT
0.65 ( ) 0.56 ( )
ER+ and/or PgR+
TNBC
0.82 ( ) 0.43 ( )
Prior platinum
No prior platinum
0.67 ( )
0.60 ( )
Response Endpoint
Olaparib CT
ORR (BICR), % CR
60 9
29 2
Median TTR, days 47 45
Median DoR, mos
6.2
7.1
BICR, blinded independent central review; BL, baseline; CT, chemotherapy; DoR, duration of response; HRQoL, health-related quality of life; TNBC, triple-negative breast cancer; TTR, time to response.
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4.

9. OlympiAD: Adverse Events Summary
Most discontinuations unrelated to AEs with olaparib or CT
Overall: 82% vs 97%
Due to AE: 4.9% vs 7.7%
Due to PD: 73% vs 75%
AE, n (%)
Olaparib
(n = 205) CT
(n = 91)
AE grade ≥ 3
75 (36.6)
46 (50.5)
Death
1 (0.5)
1 (1.1)
AE-related dose reduction
52 (25.4)
28 (30.8)
AE-related dose interruption/delay
72 (35.1)
25 (27.5)
AE-related tx d/c
10 (4.9)
7 (7.7)
Median duration of tx, mos
8.2
3.4
AE, adverse events; CT, chemotherapy; d/c, discontinuation; PD, progressive disease; tx, treatment; WBC, white blood cell.
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4.

10. OlympiAD: Adverse Events
Any-Grade AEs in ≥ 15% of Pts
Grade ≥ 3 AEs in ≥ 2% of Pts
Nausea
Anemia
Vomiting
Fatigue
Neutropenia
Diarrhea
Headache
Cough
Decreased white blood cells
Decreased appetite
Pyrexia
Increased ALT
Increased AST
Hand-foot syndrome 58 40 30 29 27 21 20 17 16 14 11 9 1 35 26 15 23 50 22 7 21 12 18 17
Anemia
Neutropenia
Decreased white blood cells
Fatigue Leukopenia
Decreased platelet count
Increased AST
Dyspnea
Headache
Hand-foot syndrome 16 9 3 2 1 4 26 10 1 3 2
AE, adverse event; ALT, alanine aminotransferase; AST, aspartate aminotransferase; CT, chemotherapy.
Olaparib CT
Olaparib CT 75 50 25 25 25 50 75 75 50 25 50 75
AEs (%)
AEs (%)
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4. Reproduced with permission.

11. OlympiAD: Investigator Conclusions
Olaparib monotherapy associated with significantly prolonged PFS vs CT in pts with HER-negative, gBRCA-mutated MBC
Median PFS: 7.0 vs 4.2 mos (HR: 0.58; P = .0009)
Olaparib showed lower rates of AE-related discontinuations and grade ≥ 3 AEs
Grade ≥ 3 AEs: 36.6% vs 50.5% with CT
This is the first phase III trial showing benefit of oral PARP inhibitor vs active comparator in MBC
AE, adverse event; CT, chemotherapy; gBRCA, germline BRCA; MBC, metastatic breast cancer
Slide credit: clinicaloptions.com
Robson ME, et al. ASCO Abstract LBA4.

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