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PURPOSE This phase III, multicenter, randomized, open-label study investigated the efficacy and safety of nivolumab versus chemotherapy (gemcitabine [GEM] or pegylated liposomal doxorubicin [PLD]) in patients with platinum-resistant ovarian cancer. MATERIALS AND METHODS Eligible patients had platinum-resistant epithelial ovarian cancer, received ≤ 1 regimen after diagnosis of resistance, and had an Eastern Cooperative Oncology Group performance score of ≤ 1. Patients were randomly assigned 1:1 to nivolumab (240 mg once every 2 weeks [as one cycle]) or chemotherapy (GEM 1000 mg/m2 for 30 minutes [once on days 1, 8, and 15] followed by a week's rest [as one cycle], or PLD 50 mg/m2 once every 4 weeks [as one cycle]). The primary outcome was overall survival (OS). Secondary outcomes included progression-free survival (PFS), overall response rate, duration of response, and safety. RESULTS Patients (n = 316) were randomly assigned to nivolumab (n = 157) or GEM or PLD (n = 159) between October 2015 and December 2017. Median OS was 10.1 (95% CI, 8.3 to 14.1) and 12.1 (95% CI, 9.3 to 15.3) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.0; 95% CI, 0.8 to 1.3; P = .808). Median PFS was 2.0 (95% CI, 1.9 to 2.2) and 3.8 (95% CI, 3.6 to 4.2) months with nivolumab and GEM or PLD, respectively (hazard ratio, 1.5; 95% CI, 1.2 to 1.9; P = .002). There was no statistical difference in overall response rate between groups (7.6% v 13.2%; odds ratio, 0.6; 95% CI, 0.2 to 1.3; P = .191). Median duration of response was numerically longer with nivolumab than GEM or PLD (18.7 v 7.4 months). Fewer treatment-related adverse events were observed with nivolumab versus GEM or PLD (61.5% v 98.1%), with no additional or new safety risks. CONCLUSION Although well-tolerated, nivolumab did not improve OS and showed worse PFS compared with GEM or PLD in patients with platinum-resistant ovarian cancer.

Background Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p Conclusion Our results suggest that the application of an SCCC regimen such as EP or IP as first-line chemotherapy for patients with locally advanced SCCC may play a key role in OS. These findings need to be validated in future nationwide, prospective clinical studies.

The objective of this study was to estimate the frequency of possible occult metastasis through long-term survival analyses in patients with clear cell carcinoma (CCC) who had undergone complete resection. During the period of 1990-2015, 799 patients with stage I-IV CCC were identified in the TOTSG database. Of these, a total of 528 patients without a residual tumor were enrolled in the study and classified into four groups: Group 1: FIGO stage IA-IB (N=104), Group 2: FIGO stage IC1 (N=170), Group 3: FIGO stage IC2/IC3 (N=98), and Group 4: FIGO stage II-III (no residual tumor: N=156). Cumulative incidences of recurrence (CIR) and death (CID) were examined. The median age was 54, ranging from 29-87. The 5-year CIR / CID of each group were as follows: Group 1 (7.3% / 3.8%), Group 2 (14.3% / 10.2%), Group 3 (37.7% / 18.4%), and Group 4 (46.5% / 33.8%), respectively {P

The aldehyde dehydrogenase 2 (ALDH2) polymorphism rs671 (Glu504Lys) causes ALDH2 inactivation and adverse acetaldehyde exposure among Asians, but little is known of the association between alcohol consumption and rs671 and ovarian cancer (OvCa) in Asians. We conducted a pooled analysis of Asian ancestry participants in the Ovarian Cancer Association Consortium. We included seven case-control studies and one cohort study comprising 460 invasive OvCa cases, 37 borderline mucinous OvCa and 1274 controls of Asian descent with information on recent alcohol consumption. Pooled odds ratios (OR) with 95% confidence intervals (CI) for OvCa risk associated with alcohol consumption, rs671 and their interaction were estimated using logistic regression models adjusted for potential confounders. No significant association was observed for daily alcohol intake with invasive OvCa (OR comparing any consumption to none = 0.83; 95% CI = 0.58-1.18) or with individual histotypes. A significant decreased risk was seen for carriers of one or both Lys alleles of rs671 for invasive mucinous OvCa (OR = 0.44; 95% CI = 0.20-0.97) and for invasive and borderline mucinous tumors combined (OR = 0.48; 95% CI = 0.26-0.89). No significant interaction was observed between alcohol consumption and rs671 genotypes. In conclusion, self-reported alcohol consumption at the quantities estimated was not associated with OvCa risk among Asians. Because the rs671 Lys allele causes ALDH2 inactivation leading to increased acetaldehyde exposure, the observed inverse genetic association with mucinous ovarian cancer is inferred to mean that alcohol intake may be a risk factor for this histotype. This association will require replication in a larger sample.

According to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study., Background Adding bevacizumab to chemotherapy for recurrent, persistent or metastatic cervical cancer significantly improved overall survival (primary endpoint), progression-free survival and overall response rate in the randomized Phase III GOG-0240 trial. However, data for bevacizumab-containing therapy are scarce in Japanese patients with advanced cervical cancer. Methods The primary objective of the single-arm multicenter Phase II JO29569 study was to evaluate the tolerability of paclitaxel (135 mg/m2 over 24 h or 175 mg/m2 over 3 h), cisplatin (50 mg/m2) and bevacizumab (15 mg/kg), administered every 3 weeks until disease progression or unacceptable toxicity in Japanese patients with stage IVB, persistent or recurrent cervical cancer. Results The seven treated patients received a median of nine (range 7–12) bevacizumab cycles and six (range 4–12) chemotherapy cycles. None of the predefined adverse events occurred during the tolerability evaluation period. The most common all-grade adverse events were alopecia, hypertension, decreased appetite, nausea and peripheral sensory neuropathy. There were no cases of fistula. The most common grade ≥3 adverse events were hypertension, neutrophil count decreased and neutropenia. Only one patient experienced febrile neutropenia. The overall response rate was 86% (95% confidence interval, 42–100%), including a complete response in one patient. At data cutoff, disease had progressed in one patient; bevacizumab therapy was ongoing in the remaining six. Conclusions According to the specified primary objective, a regimen of cisplatin, paclitaxel and bevacizumab was tolerable in Japanese patients and demonstrated encouraging activity in this small single-arm study. Further study is warranted to confirm the safety and effectiveness of bevacizumab in Japanese patients with cervical cancer.

BACKGROUND: Angiopoietin 1 and 2 regulate angiogenesis and vascular remodelling by interacting with the tyrosine kinase receptor Tie2, and inhibition of angiogenesis has shown promise in the treatment of ovarian cancer. We aimed to assess whether trebananib, a peptibody that inhibits binding of angiopoietin 1 and 2 to Tie2, improved progression-free survival when added to carboplatin and paclitaxel as first-line therapy in advanced epithelial ovarian, primary fallopian tube, or peritoneal cancer in a phase 3 clinical trial. METHODS: TRINOVA-3, a multicentre, multinational, phase 3, double-blind study, was done at 206 investigational sites (hospitals and cancer centres) in 14 countries. Eligible patients were aged 18 years or older with biopsy-confirmed International Federation of Gynecology and Obstetrics (FIGO) stage III to IV epithelial ovarian, primary peritoneal, or fallopian tube cancers, and an ECOG performance status of 0 or 1. Eligible patients were randomly assigned (2:1) using a permuted block method (block size of six patients) to receive six cycles of paclitaxel (175 mg/m2) and carboplatin (area under the serum concentration-time curve 5 or 6) every 3 weeks, plus weekly intravenous trebananib 15 mg/kg or placebo. Maintenance therapy with trebananib or placebo continued for up to 18 additional months. The primary endpoint was progression-free survival, as assessed by the investigators, in the intention-to-treat population. Safety analyses included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, number NCT01493505, and is complete. FINDINGS: Between Jan 30, 2012, and Feb 25, 2014, 1164 patients were screened and 1015 eligible patients were randomly allocated to treatment (678 to trebananib and 337 to placebo). After a median follow-up of 27·4 months (IQR 17·7-34·2), 626 patients had progression-free survival events (405 [60%] of 678 in the trebananib group and 221 [66%] of 337 in the placebo group). Median progression-free survival did not differ between the trebananib group (15·9 months [15·0-17·6]) and the placebo group (15·0 months [12·6-16·1]) groups (hazard ratio 0·93 [95% CI 0·79-1·09]; p=0·36). 512 (76%) of 675 patients in the trebananib group and 237 (71%) of 336 in the placebo group had grade 3 or worse treatment-emergent adverse events; of which the most common events were neutropenia (trebananib 238 [35%] vs placebo 126 [38%]) anaemia (76 [11%] vs 40 [12%]), and leucopenia (81 [12%] vs 35 [10%]). 269 (40%) patients in the trebananib group and 104 (31%) in the placebo group had serious adverse events. Two fatal adverse events in the trebananib group were considered related to trebananib, paclitaxel, and carboplatin (lung infection and neutropenic colitis); two were considered to be related to paclitaxel and carboplatin (general physical health deterioration and platelet count decreased). No treatment-related fatal adverse events occurred in the placebo group. INTERPRETATION: Trebananib plus carboplatin and paclitaxel did not improve progression-free survival as first-line treatment for advanced ovarian cancer. The combination of trebananib plus carboplatin and paclitaxel did not produce new safety signals. These results show that trebananib in combination with carboplatin and paclitaxel is minimally effective in this patient population. FUNDING: Amgen. ispartof: LANCET ONCOLOGY vol:20 issue:6 pages:862-876 ispartof: location:England status: published