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To compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with standard 8-day methotrexate/folinic acid (MTX/FA) versus modified regimen.Retrospective cohort study of patients with low-risk GTN followed at Rio de Janeiro Federal University, from January/1990-December/2017 with standard 8-day MTX/FA or modified regimen (MTX administered on the 8th day rather than 7th) to avoid treatment on the weekend.From 937 patients with low-risk GTN, 538 were treated with standard MTX/FA and 98 patients received modified regimen. Both groups were comparable in age (p = .749), antecedent pregnancy (p = .221), time to initiate chemotherapy (p = .926), hCG pretreatment level (p = .112) and WHO/FIGO prognostic risk score (p = .723). Patients treated with modified MTX/FA had twice of cases of metastatic lung disease compared with the standard regimen (22.5% vs 10.6%; p = .002). The rate of remission (p = .999), number of cycles to remission in the first-line (p = .966), chemoresistance (p = .500), time to switch to second-line therapy (p = .176), need for multiagent chemotherapy (p = .084), relapse (p = .122) or death (p = .475) was the same for both MTX/FA regimen. However, although patients receiving modified MTX/FA required a higher total number of remission cycles (6 vs 5 cycles; p = .004) and longer time to remission (19 vs 16 weeks; p .001) when compared with the standard regimen, these variables showed no significant differences after multivariate logistic regression adjusted for lung metastasis.The modified 8-day MTX/FA regimen didn't compromise oncologic outcomes for women with low-risk GTN. This regimen appears to be an acceptable alternative to standard 8-day MTX/FA when treatment on weekend isn't an option.

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.

To compare the outcomes of patients with low-risk gestational trophoblastic neoplasia (GTN) treated with 8-day methotrexate (MTX) with two different regimens of folinic acid (FA).Retrospective cohort study of low-risk GTN followed at Rio de Janeiro Federal University, from January/2000-December/2019 with 8-day MTX with FA at 0.1 mg/kg versus 15 mg fixed dose.Among 667 patients with low-risk GTN, 323 were treated with FA at 0.1 mg/kg and 142 with FA at 15 mg fixed dose. The weight-based and fixed dose groups were comparable in terms of clinical profile but did differ in the hCG pretreatment level (8883 versus 5127 IU/L, p0.01) and FIGO risk score 5/6 (3.4% versus 18.3%, p0.01), respectively. Despite this, there was no difference in the remission rate in first-line treatment (76.8 versus 81%, p = 0.33), although FA at 0.1 mg/kg had a significantly higher number of chemotherapy cycles to remission (5 versus 4, p0.01), need to delay chemotherapy due to toxicity (6.8 versus 2.8%, p0.01) and time to remission, (12 versus 8 weeks, p0.01), respectively. A logistic regression analysis showed that the different FA rescue regimens appeared comparable in terms of achieving remission in first-line chemotherapy for low-risk GTN (OR:5.16, CI95%:0.84-31.64, p = 0.08).FA with 15 mg fixed dose as compared to 0.1 mg/kg of FA was associated with similar primary remission rate, relapse or death among low-risk GTN treated with 8-day MTX. This regimen is highly practical, reduces visits to health facilities, appears equally safe and may be preferable with the 8-day MTX regimen in the treatment of low-risk GTN.

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.

To evaluate the impact of periodic shortage of actinomycin-d (Act-d) in the treatment of Brazilian patients with low-risk gestational trophoblastic neoplasia (GTN) after methotrexate and folinic acid rescue (MTX/FA) resistance, treated alternately with carboplatin or etoposide as a second-line regimen.Retrospective cohort that included patients with failure of first-line MTX/FA regimen for low-risk GTN treated at Rio de Janeiro Federal University, Universidade Federal de São Paulo and Irmandade da Santa Casa de Misericórdia de Porto Alegre, from January/2010- December/2017.From 356 patients with low-risk GTN treated with MTX/FA, 75 (21.1%) developed resistance, of which 40 (53.3%) received Act-d, 23 (30.7%) carboplatin and 7 (9.3%) etoposide. Although patients treated with single-agent chemotherapy as a second-line regimen had comparable clinical and primary treatment characteristics, those treated with Act-d (80%, p = 0.033) or etoposide (71.4%, p = 0.025) had higher remission rates when compared with carboplatin (47.8%). Only 29% of patients treated with carboplatin received the chemotherapy cycles without delay compared to Act-d (98%, p 0.001) or etoposide (85%, p = 0.009). Patients treated with carboplatin had significantly more hematological toxicity, notably anemia (30.4%, p = 0.008), lymphopenia (47.7%, p 0.001) and thrombocytopenia (43.4%, p 0.001), as well as a higher occurrence of febrile neutropenia (14.4%, p = 0.044) and vomiting (60%, p 0.001) than those receiving Act-d (5%, none, 2.5%, none, 10%, respectively).Carboplatin did not have a satisfactory clinical response rate, likely due to severe hematological toxicity, which postponed chemotherapy. Our results reinforce the preference for Act-d as a second-line agent in patients with low-risk GTN after MTX/FA resistance.

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

Objective Cervical cancer represents the third most commonly diagnosed cancer and the fourth cause of cancer death in women worldwide. In the palliative scenario, the combination of paclitaxel and cisplatin is widely used. Carboplatin is also an active agent in cervical cancer, and its association with paclitaxel could represent a well-tolerated, less toxic, and effective therapeutic option. The objective of this study was to evaluate response rate, progression-free survival, overall survival, and toxicity of carboplatin and paclitaxel in first palliative line for cervical cancer. Methods A retrospective search of database at Brazilian National Cancer Institute was performed, and all patients with persistent/recurrent and advanced cervical cancer treated with paclitaxel and carboplatin in first palliative line, between August 2008 and January 2010, were included. Results A total of 153 women were enrolled. Objective responses were documented in 34.6% (5.2% of complete responses and 29.4% of partial responses). With a median follow-up of 27.8 months, the median progression-free survival was 5.2 months, and the median overall survival was 10.63 months. The most common toxicity was myelosuppression: grades 3 and 4 anemia, neutropenia, and thrombocytopenia observed in 43.0%, 17.8%, and 9.2% of the cases, respectively. Neurotoxicity was presented by 30.7% of the patients. Renal toxicity was detected in 21.9% of the patients, but only 4.0% were grade 3, and none were grade 4. Conclusions This retrospective study has demonstrated that paclitaxel-carboplatin is an active and well-tolerated regimen for the treatment of advanced cervical cancer.

Objective: Cervical cancer represents the third most commonly diagnosed cancer and is an important cause of death for women suffering with malignancies. Patients who are refractory or progressed after first-line palliative treatment have a dismal prognosis and no second-line chemotherapy is considered standard so far. Several agents have been investigated in this setting and topotecan is one of the most characterized. The objective of this study was to evaluate response rate (RR), progression-free survival (PFS), overall survival (OS) and toxicity of topotecan in second palliative line for cervical cancer. Methods: An analysis was performed of all patients with recurrent or metastatic cervical cancer treated with topotecan in second palliative line at Brazilian National Cancer Institute, between 2008 and 2010. Results: A total of 73 courses of topotecan were given in the current study (median: 3.5 cycles; range 1 - 6). Anemia was the most frequent adverse event (grade 2:35%; grade 3:30%). Of the 20 patients evaluable, there were 2 partial responders to the treatment. The overall response rate (ORR) was 10%; 3 patients (15%) had stable disease as maximum response. The median PFS for the entire group was 2.93 months (95% CI 2.41 - 3.45) and OS was 4.66 months (95% CI 1.21 - 8.11). Conclusion: The limited activity of topotecan schemas in second-line treatment of cervical cancer and the associated overall toxicity may not justify their use in this setting. Patients who progress after first-line treatment may be offered participation in clinical trials, other second-line agents or best supportive care measures.

Cervical cancer represents a public health problem. Currently, it is the second most common neoplasia worldwide, with approximately 85% of the cases in developing countries. Most of the patients presents with advanced disease. The treatment based on cisplatin and radiotherapy is considered standard to patients with locally advanced cervical cancer, stages IIB to IVA. However, the results are not good enough, especially in stages III e IVA, which shows five-year survival rates of 40 and 15%, respectively. The combination of cisplatin and paclitaxel (CDDP + P) is the standard treatment in first palliative line in several oncology institutions. The replacement of CDDP by carboplatin (C) is regularly done and probably presents less non-hematologic toxicity; however, there is no data in the literature related to the specific efficacy and toxicity to the combination of C + P in this context. At INCA, the combination of C + P has been the standard treatment in first palliative line since August 2008. Objectives To evaluate response rate (RR), progression-free survival (PFS), overall survival (OS) and toxicity of patients with recurrent or metastatic cervical cancer treated with C + P. Material and methods A retrospective analysis of cervical cancer patients treated with C + P in first palliative line at INCA, between August 2008 and January 2010. Results A total of 154 patients were enrolled in the study. The most frequent histology was squamous carcinoma and 51.3 % of the patients were diagnosed as stages III and IV. 50% of the patients received 6 or more cycles of C + P as first palliative line. Objective responses were documented in 35.1% (5.2% complete responses plus 29.9 % partial responses). The median PFS and OS was 4.07 (IC95% 2.8 – 5.3) and 8.4 (IC95% 6.2 – 10.7) months respectively. Hematologic toxicity was the most common: Grade 3 and 4 anemia, neutropenia and thrombocytopenia were 42.2%, 18.1% and - 9.1%, respectively. Conclusion Indirect comparison with published data of the prospective trial using CDDP + P our results were only slightly different, probably related to differences in patients clinical and demographics data. Disclosure All authors have declared no conflicts of interest.

16559 Background: Carcinoma of the uterine cervix is one of the most common malignancies among women. The relative proportion and absolute incidence of cervical adenocarcinoma (AC) compared with sq...