PURPOSE A phase II study (ClinicalTrials.gov identifier: NCT00628251 ) showed activity of olaparib capsules versus pegylated liposomal doxorubicin in patients with germline BRCA-mutated platinum-resistant or partially platinum-sensitive relapsed ovarian cancer. We conducted a phase III trial (SOLO3) of olaparib tablets versus nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy. PATIENTS AND METHODS In this randomized, open-label trial, patients were randomly assigned 2:1 to olaparib 300 mg twice a day or physician’s choice single-agent nonplatinum chemotherapy (pegylated liposomal doxorubicin, paclitaxel, gemcitabine, or topotecan). The primary end point was objective response rate (ORR) in the measurable disease analysis set assessed by blinded independent central review (BICR). The key secondary end point was progression-free survival (PFS) assessed by BICR in the intent-to-treat population. RESULTS Of 266 randomly assigned patients, 178 were assigned to olaparib and 88 to chemotherapy. In patients with measurable disease (olaparib, n = 151; chemotherapy, n = 72), the BICR-assessed ORR was significantly higher with olaparib than with chemotherapy (72.2% v 51.4%; odds ratio [OR], 2.53 [95% CI, 1.40 to 4.58]; P = .002). In the subgroup who had received 2 prior lines of treatment, the ORR was 84.6% with olaparib and 61.5% with chemotherapy (OR, 3.44 [95% CI, 1.42 to 8.54]). BICR-assessed PFS also significantly favored olaparib versus chemotherapy (hazard ratio, 0.62 [95% CI, 0.43 to 0.91]; P = .013; median, 13.4 v 9.2 months). Adverse events were consistent with the established safety profiles of olaparib and chemotherapy. CONCLUSION Olaparib resulted in statistically significant and clinically relevant improvements in ORR and PFS compared with nonplatinum chemotherapy in patients with germline BRCA-mutated platinum-sensitive relapsed ovarian cancer who had received at least 2 prior lines of platinum-based chemotherapy.

Gestational trophoblastic neoplasia (GTN) is a rare tumor that originates from pregnancy that includes invasive mole, choriocarcinoma (CCA), placental site trophoblastic tumor and epithelioid trophoblastic tumor (PSTT/ETT). GTN presents different degrees of proliferation, invasion and dissemination, but, if treated in reference centers, has high cure rates, even in multi-metastatic cases. The diagnosis of GTN following a hydatidiform molar pregnancy is made according to the International Federation of Gynecology and Obstetrics (FIGO) 2000 criteria: four or more plateaued human chorionic gonadotropin (hCG) concentrations over three weeks; rise in hCG for three consecutive weekly measurements over at least a period of 2 weeks or more; and an elevated but falling hCG concentrations six or more months after molar evacuation. However, the latter reason for treatment is no longer used by many centers. In addition, GTN is diagnosed with a pathological diagnosis of CCA or PSTT/ETT. For staging after a molar pregnancy, FIGO recommends pelvic-transvaginal Doppler ultrasound and chest X-ray. In cases of pulmonary metastases with more than 1 cm, the screening should be complemented with chest computed tomography and brain magnetic resonance image. Single agent chemotherapy, usually Methotrexate (MTX) or Actinomycin-D (Act-D), can cure about 70% of patients with FIGO/World Health Organization (WHO) prognosis risk score ≤ 6 (low risk), reserving multiple agent chemotherapy, such as EMA/CO (Etoposide, MTX, Act-D, Cyclophosphamide and Oncovin) for cases with FIGO/WHO prognosis risk score ≥ 7 (high risk) that is often metastatic. Best overall cure rates for low and high risk disease is close to 100% and > 95%, respectively. The management of PSTT/ETT differs and cure rates tend to be a bit lower. The early diagnosis of this disease and the appropriate treatment avoid maternal death, allow the healing and maintenance of the reproductive potential of these women.

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5506 Background: Data from a randomized Phase II trial (NCT00628251) of olaparib (capsules, 200 or 400 mg bid, n=32 per arm) vs pegylated liposomal doxorubicin (PLD, n=33) in gBRCAm OC pts with recurrence ≤12 months after prior platinum therapy indicated efficacy for olaparib (Kaye et al. JCO 2012). However, the efficacy of PLD was higher than previously reported in this setting. We led a confirmatory Phase III, open-label study of olaparib vs non-platinum chemotherapy in gBRCAm PSR OC pts (NCT02282020). Methods: Pts were randomized (2:1) to olaparib tablets (300 mg bid) or chemotherapy treatment of physician’s choice (TPC) (paclitaxel [P; 80 mg/m2 on day 1 (D1), D8, D15, D22 every 4 weeks (q4w)], topotecan [T; 4 mg/m2 D1, D8, D15 q4w], gemcitabine [G; 1000 mg/m2 D1, D8, D15 q4w] or PLD [50 mg/m2 D1 q4w]) until progression, stratified by: TPC, prior lines of chemotherapy (2–3 vs ≥4) and platinum-free interval (6–12 vs >12 months). Primary endpoint: ORR (blinded independent central review [BICR]). Secondary endpoints included PFS and safety. Results: 266 gBRCAm PSR OC pts were randomized (olaparib, n=178; TPC, n=88 [ PLD, n=47; P, n=20; G, n=13; T, n=8]); 12 in the TPC arm withdrew before receiving study treatment. 223 pts (84%) had baseline BICR measurable disease (olaparib, n=151; TPC, n=72). ORR was 72% with olaparib vs 51% with TPC (OR 2.53, 95% CI 1.40–4.58; P=0.002). HR for PFS by BICR was 0.62 (95% CI 0.43–0.91; P=0.013; median 13.4 vs 9.2 months [olaparib vs TPC]) and by investigator assessment was 0.49 (95% CI 0.35–0.70; P<0.001; median 13.2 vs 8.5 months, respectively). Most common adverse events (AEs) with olaparib were nausea (65% vs 34% [TPC]) and anemia (50% vs 25%) and with TPC were palmar-plantar erythrodysesthesia (PPE; 36% vs 1% [olaparib]) and nausea. Most common grade ≥3 AEs in either arm were anemia (21% [olaparib] vs 0 [TPC]), PPE (0 vs 12%) and neutropenia (6% vs 11%). For olaparib vs TPC, serious AEs were reported by 24% vs 18% and AEs led to treatment discontinuation in 7% vs 20%. Conclusions: Pts with gBRCAm PSR OC receiving olaparib monotherapy had a significant, clinically relevant improvement in ORR and PFS vs TPC, with no new safety signals. Clinical trial information: NCT02282020.

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