Long-term Follow-up of Olaparib Maintenance Monotherapy in Platinum-Sensitive Serous Ovarian Cancer CCO Independent Conference Coverage* of the 2016 ASCO Annual Meeting, June 3 - June 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. This activity is supported by educational grants from Amgen, Ariad, Bayer Healthcare Pharmaceuticals, Celgene Corporation, Genentech, Incyte, Merck, and Taiho Pharmaceuticals.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: Background Olaparib: potent, oral PARP inhibitor Traps PARP at damaged DNA, blocking base-excision repair and results in collapse of replication forks, accumulation of double-strand breaks in DNA[1] Currently FDA approved for pts with BRCA-mutated ovarian cancer after ≥ 3 lines of chemotherapy Phase II randomized, double-blind Study 19 showed significant improvement in PFS, TFST, and TSST in pts with ovarian cancer receiving olaparib maintenance monotherapy vs placebo; greatest benefit in pts with BRCA- mutation[2,3] Overall: Median PFS (olaparib vs placebo) 8.4 vs 4.8 mos (HR: 0.35, P < .0001) BRCA-mutant: Median PFS (olaparib vs placebo) 11.2 vs 4.3 mos (HR: 0.18, P < .0001) Current report is third interim analysis of OS in Study 19[4] HRR, homologous recombination repair; PARP, poly ADP ribose polymerase; TFST, time to first subsequent therapy; TSST, time to second subsequent therapy or death 1. Murai J, et al. Cancer Res. 2012;72:5588-5599. 2. Ledermann J, et al. New Engl J Med. 2012;366:1382-1392. 3. Ledermann J, et al. Lancet Oncol. 2014;15:852-861. 4. Ledermann JA, et al. ASCO 2016. Abstract 5501. Slide credit: clinicaloptions.com

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: Study Design Platinum-sensitive, recurrent high grade serous ovarian cancer; ≥2 prior platinum-based regimens with CR/PR to most recent platinum-based therapy (N = 265) Olaparib 400 mg BID, capsules (n = 136) Treatment until disease progression Placebo BID, capsules (n = 129) Primary endpoint: PFS (RECIST 1.0) Secondary endpoints: OS, safety, tolerability Exploratory endpoints: time to first subsequent therapy or death (TFST), time to second subsequent therapy or death (TSST) Current report: descriptive updated OS analysis at 77% data maturity Study 19 not designed to evaluate OS with statistical significance OS P values deemed nominal for descriptive analysis Type 1 error rate for subgroup analyses with no pre-specified rules BID, twice daily; TFST, time to first subsequent therapy; TSST, time to second subsequent therapy or death. Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: OS OS*, Overall Study Population† (N = 265) Olaparib (n = 136) Placebo (n = 129) Deaths, n (%) 94 (69) 109 (84) Median OS, mos 29.8 27.8 HR: 0.73 (95% CI 0.55-0.96); Nominal P = .02483‡ OS*, BRCAm Subgroup† (n = 136) Olaparib (n = 74) Placebo (n = 62) Deaths, n (%) 47 (64) 48 (77) Median OS, mos 34.9 30.2 HR: 0.62 (95% CI: 0.41-0.94); Nominal P = .02480‡ OS*, BRCAwt Subgroup† (n = 118) Olaparib (n = 57) Placebo (n = 61) Deaths, n (%) 43 (75) 56 (92) Median OS, mos 24.5 26.6 HR: 0.83 (95% CI: 0.55-1.24); Nominal P = .037 *Cox proportional hazards analysis; †Data maturity 77% for overall population, 70% for BRCAm, and 84% for BRCAwt at cut-off September 30, 2015; ‡Does not meet criterion for statistical significance (P < .0095) Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: OS Restricted means analysis performed because of insufficient evidence to dismiss the proportional hazards assumption for OS[1,2] Difference in mean survival strengthens olaparib OS advantage BRCAm patients demonstrated greatest OS advantage No inconsistency between OS data for somatic BRCAm subgroup and OS data for BRCAm, germline BRCAm, or overall population, however, conclusions limited by sample size (n = 20) OS Overall study population (N = 265) BRCAm subgroup (n = 136) Olaparib Placebo (n = 129) (n = 74) (n = 62) Restricted mean OS, mos 40.1 34.9 44.3 36.9 Difference in restricted mean OS, mos (95% CI) 5.2 (-0.8 to 11.2) 7.4 (-1.1 to 16.0) 1. Grambsch P, et al. Biometrika. 1994;81:515-520. 2. Anderson PK, et al. Lifetime Data Anal. 2004;10:335-350. 3. Ledermann JA, et al. ASCO 2016. Abstract 5501. Slide credit: clinicaloptions.com

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: TFST by BRCA Subgroup TFST, BRCAm Subgroup* (n = 136) Olaparib (n = 74) Placebo (n = 62) TFST events, n (%) 53 (72) 59 (95) Median TFST, mos 15.6 6.2 HR: 0.32 (95% CI: 0.22-0.48); P < .00001 TFST, BRCAwt Subgroup* (n = 118) Olaparib (n = 57) Placebo (n = 61) TFST events, n (%) 47 (82) 60 (98) Median TFST, mos 12.9 6.9 HR: 0.45 (95% CI: 0.30-0.66); P = .00006 TFST, time to first subsequent therapy. *Maturity 82% for BRCAm and 91% for BRCAwt Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: TSST by BRCA Subgroup TSST, BRCAm Subgroup* (n = 136) Olaparib (n = 74) Placebo (n = 62) TSST events, n (%) 52 (70) 59 (90) Median TSST, mos 22.0 15.3 HR: 0.41 (95% CI: 0.28-0.62); P = .00001 TSST, BRCAwt Subgroup* (n = 118) Olaparib (n = 57) Placebo (n = 61) TSST events, n (%) 47 (82) 59 (97) Median TSST, mos 17.0 14.7 HR: 0.63 (95% CI: 0.43-0.94); P = .02263 TSST, time to second subsequent therapy or death. 14 pts with BRCAm disease from placebo arm (23%) received post- discontinuation PARP inhibitor treatment *Maturity 79% for BRCAm and 90% for BRCAwt Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: Long-term Tx Exposure Median follow-up: 5.9 yrs 15 patients (11%) still receiving olaparib 8 BRCAm 7 BRCAwt 1 patient (< 1%) still receiving placebo (BRCAm) Patients who received olaparib for ≥ 5 years Overall population: 13% BRCAm subgroup: 15% BRCAwt: 12% Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Olaparib vs Placebo in Relapsed Serous Ovarian Cancer: Safety Overall safety population: no new safety findings[1,2] 3 cases of MDS/AML (unchanged since 2012 report): 2 cases in olaparib arm (57 mos and 10 mos on treatment),1 case in placebo arm (44 mos) Rate of common AEs (anemia, fatigue, nausea, vomiting) in pts receiving olaparib ≥ 2 yrs consistent with overall population; most initially reported during first 2 yrs[1,2] Adverse Event, % Overall (N = 265) Treatment ≥ 2 yrs (n = 37) Olaparib (n = 136) Placebo (n = 128) (n = 32) (n = 5) Any AE 97 93 94 100 Any grade ≥3 AE 43 22 47 20 Dose reductions due to AE 25 4 Discontinuation due to AE 6 2 9 AML, acute myeloid leukemia; MDS, myelodysplastic syndrome. 1. Ledermann J, et al. New Engl J Med. 2012;366:1382-1392. 2. Ledermann J, et al. Lancet Oncol. 2014;15:852-861. 3. Ledermann JA, et al. ASCO 2016. Abstract 5501. Slide credit: clinicaloptions.com

Olaparib vs Placebo in Serous Ovarian Cancer: Conclusions OS advantage in pts with platinum-sensitive ovarian cancer who received olaparib maintenance vs placebo in Study 19 (HR: 0.73) OS advantage most evident in BRCAm patients with a HR of 0.62 Criterion for statistical significance (P < .0095) not met at this analysis Substantially prolonged TFST and TSST in olaparib arm, with greatest benefit seen in BRCAm pts Long-term exposure to olaparib unprecedented 13% of all pts, including 15% of BRCAm pts, received 5 or more years of maintenance olaparib No new safety findings during 3 years of additional follow-up since previous analysis TFST, time to first subsequent therapy; TSST, time to second subsequent therapy or death. Slide credit: clinicaloptions.com Ledermann JA, et al. ASCO 2016. Abstract 5501.

Go Online for More CCO Coverage of ASCO 2016! Short slideset summaries of all the key data Additional CME-certified analyses with expert faculty commentary on all the key studies in: Breast, Genitourinary, and Lung cancers Hematologic malignancies Immunotherapy clinicaloptions.com/oncology