bluuebunny/crossref_metadata_2025_split huggingface dataset:
Efficacy and long-term safety with bevacizumab included in neoadjuvant and adjuvant therapies in patients with advanced ovarian cancer: Results of the ANTHALYA trial.
Authors: Joly Florence , Cottu Paul H. , Gouy Sebastien , Lambaudie Eric , Selle Frédéric , Leblanc Eric , Floquet Anne , Pomel Christophe , Chereau Elisabeth , Zohar Sarah , Dupin Julien , Balouet Sabine , Ferri Rose-Marie , Urbieta Marisol , Kockler Leila , Rouzier Romain 
Published: September 2018

5538 Background: ANTHALYA showed that neoadjuvant Bevacizumab (B) added to Carboplatin and Paclitaxel (CP) was well tolerated and achieved encouraging complete resection rates at IDS (58.6%) in unresectable FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma (EJC 2017;70:133–42). We report response rates, PFS and long-term safety. Methods: Patients (pts) in ANTHALYA were randomized 2:1 to 4 cycles (c) of neoadjuvant CP ±3 c of B (15 mg/kg), IDS for eligible patients, then 1 c of CP + 3 c CPB + 21 c of B. Response and progression were evaluated by RECIST 1.1 using CT scan and CA-125. Circulating tumor cell counts (CTC) were evaluated at baseline, c2 and IDS. Results: 95 pts were treated in CP (n=37) or BCP (n=58) groups (mean study duration were 16.1 months [mo] and 16.9 mo, respectively). 80 pts (CP: 81% / BCP: 88%) had a CA-125 response (50% reduction in CA-125 level) before IDS. Objective response rates were 65% (62% CP / 67% BCP) before IDS (28 days after c4), 46% at c8 (46% CP/ 47% BCP) and 19% at c26 (19% CP/ 19% BCP). 24 (64.9%) CP pts and 26 (44.8%) BCP pts progressed during follow up (median PFS 21.2 mo [95%CI: 14.5, 26.7] and 23.5 mo [18.5, 30.6], respectively). Median PFS was respectively: 25.8 mo (21.0, 30.0) and 17.1 mo (13.5, 22.2) for pts with/without complete resection at IDS; 21.0 mo (15.0, 25.4) and 25.8 mo (18.5, 27.2) for pts with/without baseline CTCs (n=29 / 59); 21.8 mo (17.5, 27.1) and 22.2 mo (15.3, 38.0) for pts with FIGO IIIC and IV tumors. 36 pts did not receive adjuvant therapy within the study (21 were unresectable for IDS), 59 pts (57% CP / 66% BCP) received it. Of those, 34 pts (52% CP / 61% BCP) had Grade ≥3 adverse events including neutropenia (29% CP / 34% BCP), HBP (10% CP / 8% BCP), proteinuria (10% CP / 0% BCP), deep venous thrombosis (5% CP / 3% BCP), pulmonary embolism (0% CP / 8% BCP). Conclusions: Neoadjuvant BCP followed by IDS and adjuvant BCP achieves high response rates and extended PFS with an acceptable toxicity in this specific population of pts with FIGO stage IIIC/IV ovarian, tubal or peritoneal adenocarcinoma not eligible for primary debulking surgery. IDS outcome and CTC counts should be further explored as long term prognostic factors. Clinical trial information: NCT01739218.
Safety findings from FORWARD II: A Phase 1b study evaluating the folate receptor alpha (FRα)-targeting antibody-drug conjugate (ADC) mirvetuximab soravtansine (IMGN853) in combination with bevacizumab, carboplatin, pegylated liposomal doxorubicin (PLD), or pembrolizumab in patients (pts) with ovarian cancer.
Authors: O'Malley David M. , Moore Kathleen N. , Vergote Ignace , Martin Lainie P. , Gilbert Lucy , Gonzalez Martin Antonio , Nepert Dale L. , Ruiz-Soto Rodrigo , Birrer Michael J. , Matulonis Ursula A. 
Published: September 2018

5553 Background: FORWARD II is a phase 1b study of the FRα-targeting ADC, mirvetuximab soravtansine (IMGN853), in combination with bevacizumab (BEV), carboplatin, PLD, or pembrolizumab in adults with FRα-positive EOC, primary peritoneal, or fallopian tube tumors (NCT02606305). Methods: The escalation stage of this trial evaluated the safety and tolerability of IMGN853 as part of 4 combination regimens: IMGN853 + BEV; + carboplatin; + PLD; and + pembrolizumab. IMGN853 was administered in combination on Day 1 of a 21 (BEV or carboplatin) or 28-day cycle (PLD). Pembrolizumab escalation is continuing. The starting dose of IMGN853 was 5 mg/kg (adjusted ideal body weight, AIBW), one level lower than the recommended single agent phase 2 dose (RP2D; 6 mg/kg AIBW) defined in a first-in-human study (NCT01609556). Adverse events (AEs) were evaluated by CTCAE v4.0. Results: 46 pts enrolled in the first 3 cohorts. IMGN853 was escalated from 5 to 6 mg/kg. Carboplatin and PLD dosing were escalated from AUC4 to AUC5 and 30 to 40 mg/m2, respectively; BEV dosing remained constant at 15 mg/kg. Diarrhea, nausea, and fatigue were common across cohorts (all grades; 33-57%) and mostly low grade (i.e. ≤ 2), consistent with the IMGN853 safety profile from the earlier phase I monotherapy study. AEs of interest related to the combination agents were seen in each arm. For example, grade 1/2 proteinuria (36%) and grade 3 hypertension (21%) were only observed in the BEV combination. Thrombocytopenia (44%) and neutropenia (39%), grades 1-3, occurred most frequently in the carboplatin arm. Grade 3 anemia and vomiting (each 14%), as well as low grade (≤ 2) constipation (43%), were seen in the PLD cohort. Conclusions: The RP2D dose of IMGN853 was readily combined with the highest doses (as per protocol) of BEV, carboplatin, and PLD. The AE profiles for these combinations were manageable and as expected based on known profiles of each agent; importantly, no new safety signals were identified. Updated data from all 4 combination regimens will be presented. Clinical trial information: NCT02606305.
The successful phase 3 niraparib ENGOT-OV16/NOVA trial included a substantial number of patients with platinum resistant ovarian cancer (OC).
Authors: Del Campo Jose Maria , Mirza Mansoor Raza , Berek Jonathan S. , Provencher Diane M. , Emons Guenter , Fabbro Michel , Lord Rosemary , Colombo Nicoletta , Petru Edgar , Wenham Robert Michael , Herrstedt Jorn , Gilbert Lucy , Heubner Martin Leonhard , Gonzalez Martin Antonio , Follana Philippe , Benigno Benedict B. , Dørum Anne , Rimel Bj , Hazard Sebastien , Matulonis Ursula A. ,   For the ENGOT-OV16/NOVA Investigators
Published: September 2018

5560 Background: Niraparib is a highly selective poly (ADP-ribose) polymerase (PARP) 1/2 inhibitor (PARPi); in preclinical studies, it concentrates in the tumor relative to plasma to deliver durable, near complete PARP inhibition and persistent antitumor effects.Niraparib demonstrated significantly longer progression free survival (PFS) vs placebo in patients (pts) with recurrent OC who were randomized following a complete response (CR) or partial response (PR) to platinum based chemotherapy in the controlled, double-blind phase 3 ENGOT-OV16/NOVA trial. To more fully characterize the NOVA trial population, we assessed platinum resistance status, defined as a duration of response to platinum < 6 months to the most recent (ultimate) platinum regimen. Analysis was limited to pts in the placebo arm, as inclusion of pts receiving active treatment (niraparib) would have confounded the ability to determine duration of response to platinum alone. Methods: Pts with recurrent OC, no prior PARPi use, ≥2 prior courses of platinum based chemotherapy, and CR or PR to the most recent platinum based chemotherapy were eligible. Pts were assigned to one of two cohorts based on g BRCA testing (g BRCAmut or non-g BRCAmut) and randomized 2:1 within each cohort to niraparib 300 mg or placebo qd until progressive disease (PD). Randomization occurred up to 8 weeks following the last dose of the most recent platinum based chemotherapy. PFS was measured from time of randomization to death or earliest PD as assessed by independent review committee. Estimated probability of pts having disease progression in each cohort and pooled across cohorts 6 months after the last dose of their most recent platinum therapy was calculated using the Kaplan-Meier methodology. Results: 181 pts were randomized to placebo (65 g BRCAmut and 116 non-g BRCAmut). Platinum resistance rate estimates for the g BRCAmut, non-g BRCAmut, and pooled cohorts were 42%, 53%, and 49%, respectively. Conclusions: Approximately half of the pts in the NOVA study, where niraparib treatment met its primary endpoint of prolonging PFS following a response to platinum, had developed platinum resistance to their last line of chemotherapy. Clinical trial information: NCT01847274.
Prognostic implications of lymph node metastasis in advanced ovarian cancer: Analysis of National Cancer Database.
Authors: Saha Sukamal , Ramanathan Sabarina , Mukkamala Suresh , Salib Hayman S. , Oza Rajen , Lee Jeen , Bajaj Vinay , Arora Madan L. , Wiese David 
Published: September 2018

5567 Background: During debulking surgery (Surg) for advanced ovarian cancer (OvCa), lymph node (LN) sampling are not routinely performed. Hence, prognostic implications of LN involvement following debulking surg and chemotherapy (ChemoRx) were analyzed from National Cancer Database (NCDB). Methods: Only Stage III and Stage IV patients (pts) from 2004 –2014 NCDB pts undergoing Debulking surg. and ChemoRx were included. Group A included pts with debulking surg without bowel resection; Group B with major bowel resection and Group C with bowel and bladder resection. Pts were further subdivided according to the use of 1) NeoAdjuvant (NeoAdj) 2) Adjuvant (Adj) and 3) Neo Adj and Adj ChemoRx. Survival analysis was done based on -ve or +ve LN status. using Pearson Chi Square testing. Results: Out of 10,737 Stage III and 3,102 Stage IV pts, there were 6828 Group A, 6413 Group B and 598 Group C pts. Five year overall survival (OS) for all pts in Stage III with LN-ve vs LN +ve was 59.9% vs 53.9% and Stage IV was 48.7% vs 41.2%. In Group A, B, and C, the 5 yr OS was better in LN – ve than LN +ve pts (Table1). The OS for both LN –ve and LN +ve groups were better in Adjuvant chemoRx in all 3 groups. OS was slightly better in Stage III vs Stage IV pts. Conclusions: Even though LN dissection are not routinely done during debulking surg, overall pts with LN metastasis do worse than LN –ve pts irrespective of the timing of ChemoRx. Hence, LN sampling during debulking surg should be strongly considered as it may provide important prognostic information. [Table: see text]
INNOVATE: A phase II study of TTFields (200 kHz) concomitant with weekly paclitaxel for recurrent ovarian cancer—Updated safety and efficacy results.
Authors: Vergote Ignace , Moos Roger von , Manso Luis , Sessa Cristiana 
Published: September 2018

5580 Background: TTFields are a non-invasive, regional antimitotic treatment modality, which have been approved for the treatment of recurrent and newly diagnosed glioblastoma by the FDA. TTFields act by delivering intermediate frequency alternating electric fields to the tumor, predominantly by disrupting the formation of the mitotic spindle during metaphase. INNOVATE was the first trial testing TTFields (200kHz) in ovarian cancer patients. Methods: Thirty-one recurrent, platinum-resistant, unresectable ovarian cancer patients were enrolled in the INNOVATE trial and treated with TTFields in combination with weekly paclitaxel. The primary endpoint was treatment emergent adverse events. Secondary endpoints included progression free-survival, overall survival and radiological response rate. Results: The median age was 60 (range – 45-77), most patients (77%) had serous histology. 52% had an ECOG score of 0. The median number of prior chemotherapy regimens was 4.1 (range 1-11). All patients were platinum-resistant, and 97% of patients received prior taxane-containing regimens. Ten (32%) patients suffered from serious adverse events (SAEs) during the study, none were related to TTFields. Of all reported SAEs, 31% were related to gastrointestinal disorders (ileus, jaundice and ascites) and 31% were respiratory events (dyspnea, pleural effusion and pulmonary embolism). Only one SAE which, related to the tumor, led to permanent discontinuation of the device. Most patients were reported to have mild-moderate, TTFields-related skin irritation, out of whom only two patients (6.4%) had severe-grade events. The median PFS was 8.9 months (95% CI 4.7, NA). Of the evaluable tumors, 25% had partial response and another 46.4% stable disease – a clinical benefit of 71.4%. Six patients (19.4%) had a CA 125 response, translating into a decrease of 50% or more in serum levels. The median OS was not reached. Conclusions: TTFields concomitant to weekly paclitaxel are tolerable and safe in heavily pre-treated platinum-resistant ovarian cancer ovarian cancer patients. These data support further clinical testing of TTFields with chemotherapy in ovarian cancer. Clinical trial information: NCT02244502.
Outcome of patients with advanced endometrial and cervical cancer treated in a phase 1 unit.
Authors: Miller Rowan , Devlin Michael-John , Brown Nicholas Fraser , Grunewald Tami , McCormack Mary , Lockley Michelle , Ledermann Jonathan A. , Meyer Tim , Forster Martin David , Kristeleit Rebecca Sophie 
Published: September 2018

5597 Background: Patients (pts) with advanced endometrial (EC), cervical and vulval (CVC) cancer have limited therapeutic options and poor prognosis. Early phase trials may be a suitable option for pts with good performance status aided by molecular selection. We sought to determine the outcome of EC and CVC pts treated in a phase 1 unit. Methods: Medical records of pts with EC and CVC treated within an early phase trial between 2010 and 2016 were reviewed. Data comprised pt and tumor characteristics, prior therapy, trial therapy and outcome. Results: 38 pts, median age 59 years (21-74) with EC (19) or CVC (19) were identified. Median prior therapies for advanced disease: 1 (1-3). Histological subtypes: endometrioid (4), high grade serous (HGS 7), carcinosarcoma (CS 4), clear cell (1), and adenosquamous (3) for pts with EC; adenocarcinoma (5), squamous (11), clear cell (2) and neuroendocrine (1) for CVC pts. 20 pts (53%) had Next Generation Sequencing (NGS) using a targeted panel with actionable mutations identified in 10 (KRAS (4), PIK3CA (6) and EGFR (1)). Pts were allocated in order of priority to a trial (1) on the basis of NGS (‘genomic’ 8%), (2) within a ‘tumor specific’ expansion cohort (45%) or (3) a ‘generic’ study (47%). The overall response rate (ORR) was 21% with 34% stable disease (SD) and median progression free survival (PFS) and overall survival (OS) of 11 and 42 weeks respectively, with 10 pts still on study. Within the EC cohort ORR was 21% with 32% SD and PFS and OS of 9 and 38 weeks respectively. For the CVC cohort ORR was 21% with 37% SD and PFS and OS of 12 and 42 weeks respectively. Outcomes were better for the pts in the genomic and tumour specific groups. Both PFS and OS were longer with median PFS of 42, 32 and 8 weeks and OS of 91, not reached and 37 weeks for genomic, tumor specific and generic trials respectively. Conclusions: Early phase trials represent a good option for pts with advanced EC and CVC with meaningful clinical benefit observed even in this small cohort. Encouraging RR and PFS were observed in these pts with limited standard treatment options. This includes pts with difficult to treat histological subtypes such as HGS and CS EC and clear cell and adenocarcinoma CVC. NGS is feasible in real time and increasing use may benefit pts further.
Pathologic complete response (pCR) rates after neoadjuvant pertuzumab (P) and trastuzumab (H) administered concomitantly with weekly paclitaxel (T) and 5-fluorouracil/epirubicin/cyclophosphamide (FEC) chemotherapy for clinical stage I-III HER2-positive breast cancer.
Authors: Foldi Julia , Mougalian Sarah Schellhorn , Silber Andrea , Lannin Donald R. , Killelea Brigid K. , Chagpar Anees B. , Horowitz Nina Ruth , Frederick Courtney , Rispoli Lawrence , Abu-Khalaf Maysa M. , Sabbath Kert D. , Sanft Tara Beth , Fischbach Neal A. , Brandt Debra S. , Hofstatter Erin Wysong , DiGiovanna Michael , Pusztai Lajos 
Published: September 2018

577 Background: Inclusion of H with chemotherapy has increased pathologic complete response (pCR) rates in HER2 positive breast cancer, and dual HER2 blockade involving H + P further increased efficacy. With dual HER2 blockade and taxane-based (+/-carboplatin followed by anthracycline) chemotherapies, pCR rates reach, 75% in estrogen receptor (ER) negative and 45% in ER+ patients. HER2 targeted therapies also increase the efficacy of anthracyclines but are not routinely combined due to potential cardiotoxicity. The goal of this phase II study was to assess pCR rate when H+P is administered during the entire treatment duration, including the anthracycline phase, of weekly T (80 mg/m2) x 12 followed by FE(75 mg/m2)C x 4 neoadjuvant chemotherapy. Methods: pCR (ypT0/is and ypN0) rate was assessed separately in ER+ and ER- cancers following Simon’s two-stage design to detect improvement in pCR rates to 90% and 70% in the ER- and ER+ cohorts, respectively. Eligibility included age <65, stage I-III, HER2+ disease, and normal cardiac function. Results: The ER- cohort completed full accrual of 25 patients: 23 completed therapy and surgery, 2 patients are still receiving treatment. The pCR rate is 78% (n=18, 95% CI:58-90%). The ER+ cohort was closed after 23 patients were accrued to the first stage due to lower than expected pCR of 26% (n=6, 95% CI:13-46%) at interim analysis. The incidence of grade 3/4 adverse events was 48% (n=24/50), the most common being neutropenia (n=12) and diarrhea (n=7). No patient experienced symptomatic congestive heart failure, one patient had a drop in LVEF to < 50% following completion of chemotherapy. Thirteen patients (27%) had a >10% asymptomatic drop in their LVEF but remained above 50%, LVEF returned to baseline by the next assessment in half of these cases. Conclusions: Neoadjuvant P and H administered concomitantly with weekly T followed by FEC resulted in 78% pCR rate in ER-/HER2+ cancers. This pCR rate is among the highest reported in the literature. The pCR rate was substantially lower in ER+ cancers. Clinical trial information: NCT01855828.
Phase III randomized trial of chemotherapy with or without bevacizumab (B) in patients (pts) with recurrent or metastatic squamous cell carcinoma of the head and neck (R/M SCCHN): Survival analysis of E1305, an ECOG-ACRIN Cancer Research Group trial.
Authors: Argiris Athanassios , Li Shuli , Savvides Panayiotis , Ohr James , Gilbert Jill , Levine Marshall A. , Haigentz Missak , Saba Nabil F. , Chakravarti Arnab , Ikpeazu Chukwuemeka , Schneider Charles , Pinto Harlan , Forastiere Arlene A. , Burtness Barbara 
Published: September 2018

6000 Background: The addition of B, an anti-VEGF monoclonal antibody, to chemotherapy has improved outcomes in several solid tumors. Pemetrexed plus B showed promising efficacy in R/M SCCHN (Argiris et al. JCO 2011). E1305 was designed to evaluate the addition of B to a platinum doublet in R/M SCCHN. Methods: B-eligible pts with performance status 0-1, not having received chemotherapy for R/M SCCHN (prior chemotherapy for locally advanced disease allowed ≥ 4 months) and without factors predisposing to bleeding (history of bleeding due to SCCHN, anticoagulation, central cavitary lung metastasis, carotid invasion) were randomized to: A) one of 4 regimens (investigator's choice) given every 3 weeks: A1, cisplatin (C) 100 mg/m2, 5-FU 1000 mg/m2/day x 4 days; A2, carboplatin (Cb) AUC 6, 5-FU 1000 mg/m2/day x 4 days; A3, C 75 mg/m2, docetaxel (D) 75 mg/m2; A4, Cb AUC 6, D 75 mg/m2, or B) the same regimen (B1, B2, B3, B4) plus B 15 mg/Kg IV, every 3 weeks, until progression. Chemotherapy could be stopped after 6 cycles after maximum response. All pts received prophylactic antibiotics. The primary endpoint was overall survival (OS). Control median OS of 8.5 months (mo) was projected; the addition of B was hypothesized to increase median OS to 11.5 mo with a hazard ratio (HR) of 0.74. Results: 403 pts were randomized (200 in arm A; 203 in arm B). Baseline characteristics were well balanced. 38% in arm A/42% in arm B had an oropharyngeal primary; 87% received C or Cb plus D. With a median follow-up of 23.1 mo, median OS was 11 mo in arm A and 12.6 mo in arm B; HR 0.84 (95% CI 0.67-1.05), p = 0.13. The 1-, 2-, 3-, and 4-year OS were 46% vs 51%, 18% vs 26%, 8% vs 16%, 6% vs 13%, in arm A vs B, respectively. Median PFS was 4.4 mo in arm A and 6.1 mo in arm B (HR 0.71, 95% CI 0.58-0.87; p = 0.0012). Objective response rate was 25% in arm A vs 36% in arm B (p = 0.013). Grade 3-5 bleeding occurred in 3.5% in arm A vs 7.7% in arm B (p = 0.08). Conclusions: B added to a standard platinum doublet improved response rate and PFS but not OS in first-line treatment of R/M SCCHN. The control arm in this study performed better than expected. Clinical trial information: NCT00588770.
Impact of prophylactic human papillomavirus (HPV) vaccination on oral HPV infections among young adults in the U.S.
Authors: Gillison Maura L. , Broutian Tatevik , Graubard Barry , Pickard Robert , Tong Zhen-Yue , Xiao Weihong , Kahle Lisa , Chaturvedi Anil 
Published: September 2018

6003 Background: The incidence of HPV-positive oropharyngeal cancers has risen in recent decades among US men. The potential impact of HPV vaccines on oral HPV infections has yet to be evaluated in efficacy-trials or surveillance studies. Methods: To evaluate the impact of prophylactic HPV vaccination on oral HPV infections in the US population, we conducted a cross-sectional study among men and women aged 18-33 years (n = 2,627) in the National Health and Nutrition Examination Survey, 2011-2014. We examined the effect of self-reported receipt of ≥1 vaccine dose on oral HPV infection (vaccine-types 16/18/6/11) prevalence among vaccinated vs. unvaccinated individuals. Additional outcomes included percent reduction in infection-prevalence among vaccinated individuals and population-level effectiveness of vaccination. Analyses accounted for the complex sampling design. Comparisons between vaccinated and unvaccinated individuals were conducted using binary logistic regression, with adjustment for age, gender, and race. Statistical significance was assessed using a quasi-score test. Results: During 2011-2014, 18.3% of the US population aged 18-33 years reported receipt of ≥1 HPV vaccine-dose prior to age 26 (29.2% in women and 6.9% in men; P< 0.001). The prevalence (population-weighted) of oral HPV16/18/6/11 infections was significantly reduced in vaccinated vs. unvaccinated individuals (0.11% vs. 1.61%; P= 0.008), corresponding to an estimated 88.2% (95%CI = 5.7%-98.5%) reduction in prevalence. Notably, oral HPV16/18/6/11 prevalence was significantly reduced in vaccinated vs. unvaccinated men (0.0% vs. 2.13%; P= 0.007). In contrast, prevalence for 33 non-vaccine HPV types was similar (3.98% vs. 4.74%; P= 0.24). Accounting for HPV vaccine-uptake, the population-level effectiveness of HPV vaccination on the burden of oral HPV16/18/6/11 infections was 17.0% overall, 25.0% in women and 6.9% in men. Conclusions: HPV vaccination substantially reduced vaccine-type oral HPV infection prevalence among young adults (ages 18-33 years) in the US population during 2011-2014. However, due to low vaccine uptake, population-level effectiveness was modest overall and particularly low in men.