bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preoperative chemotherapy for advanced endometrial cancer-registry analysis of outcomes.
Authors: Salamekh Samer , Yan Jingsheng , Zhu Hong , Albuquerque Kevin V. 
Published: May 2020

6088 Background: Hysterectomy followed by risk-adjusted adjuvant treatment is the standard of care for staging and treatment of locally advanced endometrial cancer. Up-front surgery is difficult in some locally advanced cases with extensive local invasion since negative margins may not be achievable. Pre-operative systemic treatment may be used to shrink the tumor and facilitate resection, echoing the experience from ovarian cancer. There is limited data for this paradigm in endometrial cancer. Methods: The National Cancer Database (NCDB) was queried for cases with FIGO stage III/IV endometrial cancer (serous, clear cell, or endometrial histology) who underwent surgery and had known chemotherapy/radiation sequencing. Those who received pre-operative chemotherapy +/- post-operative chemotherapy (PreCT) were compared to those who received post-operative chemotherapy alone (PostCT). PreCT cases were considered to be initially borderline resectable or unresectable. Downstaging was determined by comparing clinical and pathologic T-stage. Univariable (UV) and multivariable (MV) analyses were performed, with statistically significant values reported. Results: 12,310 cases in PostCT and 1,059 cases in PreCT were included in the analysis. Pre-CT cases were more likely to have higher AJCC T-stage, clinically positive nodes, serous histology, higher grade, and positive surgical margins (28% compared to 16%). Overall survival (OS) was lower for PreCT compared to PostCT (HR = 2.18 UV; HR = 1.87 MV). 20% of patients who received PreCT were down-staged compared to 2% in PostCT group. Patients who were downstaged with PreCT were more likely to achieve negative margins (OR 0.36 UV) and had improved OS compared to those whose stage did not change (HR = 0.61 UV; HR = 0.37 MV). Positive margins portended worse OS for both PreCT (HR = 1.93 UV) and PostCT (HR = 2.63 UV). Negative margins in PreCT had improved OS compared to positive margins in PostCT (HR = 1.2 UV; 2.67 MV). Post-operative radiation benefited both PreCT (HR = 0.45 UV; HR = 0.34 MV) and PostCT groups (HR = 0.48 UV; HR 0.64 MV). Conclusions: Preoperative chemotherapy increased the number of patients who were downstaged and those who were downstaged were more likely to achieve a negative margin. Patients who achieved negative margins in PreCT had improved OS compared to those with positive margins in PostCT. Adjuvant radiation further improved OS in both cohorts. Pre-operative chemotherapy can be considered for patients with unresectable/borderline resectable locally advanced endometrial cancer.
Equivalence randomized trial comparing treatment based on sentinel node biopsy versus neck dissection in operable T1-T2N0 oral and oropharyngeal cancer.
Authors: Garrel Renaud , Perriard Françoise , Favier Valentin , Richard Fanny , Daures Jean Pierre , De Boutray Marie 
Published: May 2020

6501 Background: Although sentinel node (SN) biopsy is known to be accurate in operable oral and oropharyngeal cT1-T2N0 squamous cell carcinomas (OC), the oncological equivalence of a treatment based on SN compared to that based on neck dissection (ND) has to be evaluated. Methods: A prospective multicenter randomized medico economic study included patients with OC operated of primary tumor and systematic neck dissection in ND-arm (standard treatment) versus patients operated of primary tumor and SN biopsy only if negative or ND if SN biopsy positive (SN-arm, experimental treatment). Primary endpoint was neck-relapse-free survival at 2 years and 5 years. Hypothesis of equivalence was tested with a delta of 10%. Functional outcomes were assessed by comparing the length of the hospital stay, the number of physiotherapy prescriptions and dysfunctions in neck and shoulder scales during the 2 post-operative years. Results: Out of 307 included patients in 10 hospital centers, 279 evaluable cases showed a neck-relapse-free survival at 2 years and 5 years respectively of 89,6% (95%CI: 0.827; 0.938) and 89,6 %, (95%CI: 0.827; 0.938) in the ND-arm (14 neck relapses out of 139 patients) and of 90,7% (95%CI: 0.842; 0.946) and 89,4% (95%CI: 0.823; 0.938) in the SN-arm (13 neck relapses out of 140 patients). The survival difference between the two arms was less than the 10% expected interval, confirming the equivalence with p = 0.008. The median length of hospital stay was 7 days (ext. 3-30) in SN-arm and 8 days (ext. 2-94) in ND-arm (Wilcoxon’s test, p = 0.001). The other functional outcomes were statistically worse in the ND-arm at the 2nd, 4th and 6th postoperative months. There was no more difference at 12 months and later. Conclusions: This study demonstrated the oncological equivalence of the SN approach compared to the ND approach in a multicenter study with a lower morbidity and care consumption in the SN approach during the 6 first post-operative months. Treatment based on sentinel node biopsy is established as a standard of care in OC. Clinical trial information: NCT02855723 .
Atezolizumab combinations with targeted therapy for anaplastic thyroid carcinoma (ATC).
Authors: Cabanillas Maria E. , Dadu Ramona , Ferrarotto Renata , Liu Suyu , Fellman Bryan M. , Gross Neil D. , Gule-Monroe Maria , Lu Charles , Grosu Horiana , Williams Michelle D. , Duose Dzifa Yawa , Mallampati Saradhi , Dervin Shannon , Mckenna Edward Francis , Wang Rui Jennifer , Zafereo Mark , Busaidy Naifa Lamki 
Published: May 2020

6514 Background: ATC is a rare/aggressive cancer with dismal outcome. Dabrafenib/trametinib is approved for BRAF-mutated ATC but pts eventually develop resistance. There are no approved drugs for pts with BRAF-wild type ATC. Better treatments (tx) are needed. Methods: ATC pts with PS < 3 enrolled on a prospective trial at a single center, and tx was assigned by driver mutation: BRAF (cohort 1), RAS, NF1, or NF2 (cohort 2), or none of these (cohort 3). Cohort 4 with paclitaxel was exploratory for pts who did not qualify for 1-3. All pts received atezolizumab (A) IV + targeted therapy. Cohort 1 had run-in with vemurafenib (V) 960mg BID/cobimetinib (C) 60mg QD po for 28 days, followed by A 840mg Q2 weeks, at which time V dose was decreased to 720mg BID. Cohort 2: A + C (same doses as cohort 1); cohort 3: A 1200 mg Q3 weeks + bevacizumab 15 mg/kg q3 weeks. Pts unable to swallow used alternative drug preparation (ADP; crushed vemurafenib, suspension cobimetinib). Primary objective is to determine whether the tx in cohorts 1-3 leads to improved overall survival (OS). The trial was designed to enroll 36 pts but we are reporting early due to positive findings. Response rate (RR) was measured by RECISTv1.1. Median OS was estimated by Kaplan-Meier method. cfDNA and biopsy were obtained at baseline, course 2 and progression. Pts were allowed to undergo surgery and radiation while on trial. Results: From August 2017-January 2020, 34 ATC pts were enrolled in cohorts 1-3 and 9 in cohort 4. Cohort 3 closed early for futility. 3 pts had ADP. Median follow-up time was 7.51 mos (range: 0.43 – 27.37). Median OS in cohorts 1-3 was 18.23 mos (CI 10.45-NE) and 1-year OS was 67% (95%CI: 45%, 82%). See table. Response rate (RR) in cohort 1 was 71%: CR 1/17 (6%), PR 11/17 (65%), SD 4/17 (23%), 1 never restaged; in cohort 2 RR was 7%: PR 1/14 (7%), SD 7/14 (50%), PD 4/14 (29%), 2 died early. 8 (24% of cohort 1-3) pts had complete tumor resection after tx with VCA (n = 7) or CA (n = 1); all but 1 of these pts are alive. AEs as expected. cfDNA data will be reported at meeting. Conclusions: Atezolizumab + vemurafenib/cobimetinib for BRAF-mutated or + cobimetinib for NF1/2 or RAS-mutated ATC is effective, as evidenced by the long OS in these pts (13 mos > historical control). A significant number of patients, particularly in cohort 1, were able to undergo complete tumor resection due to a favorable response to tx. Clinical trial information: NCT03181100 . [Table: see text]
A multicenter phase II trial of the combination cisplatin/ docetaxel/durvalumab/tremelimumab as single-cycle induction treatment in locally advanced HNSCC (CheckRad-CD8 trial).
Authors: Hecht Markus , Gostian Antoniu-Oreste , Eckstein Markus , Rutzner Sandra , von der Grün Jens , Illmer Thomas , Hautmann Matthias G. , Brunner Thomas , Laban Simon , Klautke Gunther , Tamaskovics Balint , Hinke Axel , Frey Benjamin , Semrau Sabine , Hartmann Arndt , Roedel Claus , Budach Wilfried , Gaipl Udo S , Iro Heinrich , Fietkau Rainer 
Published: May 2020

6519 Background: PD-1/PD-L1 inhibitors are efficient in head and neck squamous cell cancer (HNSCC). Combination with anti-CTLA4 agents may enhance anti-tumor activity compared to anti-PD-1/PD-L1 monotherapy in different tumor types. In the CheckRad-CD8 trial the typical induction treatment consisting of Cisplatin/Docetaxel was combined with Durvalumab/Tremelimumab. Patients with pathological complete response (pCR) in the re-biopsy after induction treatment or at least 20% increase of intratumoral CD8 density in the re-biopsy compared to baseline entered radioimmunotherapy with concomitant Durvalumab/Tremelimumab. Methods: In this prospective multicenter phase II trial, patients with HNSCC stage III-IVB received a single cycle of Cisplatin 30mg/m² d1-3, Docetaxel 75mg/m² d1, Durvalumab 1500mg fix dose d5 and Tremelimumab 75mg fix dose d5. Objectives of this interim analysis were to quantify the effect of the induction treatment on intratumoral CD8 density and the pCR rate and to generate safety data. Results: Between Sep 2018 and Dec 2019, 57 patients were enrolled. Median age was 59 years, 22 patients (37%) were current smokers, 27 patients (47%) had oropharyngeal tumors (52% p16 positive). The median pre-treatment intratumoral CD8 density was 335 CD8+ cells/mm². After induction treatment 27 patients (47%) had a pCR in the re-biopsy and further 25 patients (44%) had a relevant increase of intratumoral CD8+ cells (median increase by factor 3.0). Response according to RECIST criteria was CR in 1 (2%), PR in 19 (33%) and SD in 20 patients (35%) (17 patients not evaluable). Adverse events (AE) grade 3-4 appeared in 39 patients (68%) and mainly consisted of leucopenia (43%) and infections (28%). 6 patients (11%) developed grade 3-4 immune-related AEs. In multivariable analysis the intratumoral CD8 density was the only independently significant predictor of pCR (odds ratio 1.0013 per cell/mm², 95%-CI 1.00023-1.0023, p=0.017). 42 patients (74%) continued with Durvalumab/ Tremelimumab concomitant to radiotherapy. Conclusions: Single cycle induction treatment with Cisplatin/Docetaxel/Durvalumab/Tremelimumab is feasible and achieves a high pCR rate. CD8 density may have a predictive role for further treatment planning in locally advanced HNSCC. Clinical trial information: NCT03426657 .
Association of autoimmunity with survival in patients with recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) treated with immune checkpoint inhibitors (ICIs).
Authors: Economopoulou Panagiota , Gavrielatou Niki , Papaxoinis George , Kotsantis Ioannis , Pantazopoulos Anastasios , Anastasiou Maria , Kavourakis George , Gkolfinopoulos Stavros , Psyrri Amanda 
Published: May 2020

6537 Background: ICIs are associated with immune-related adverse events (irAEs) that occur as a consequence of enhanced immune response due to T-cell activation. The objective of this observational cohort study was to investigate the association between irAEs and disease outcome in pts with R/M HNSCC. Methods: 110 pts treated with ICIs were reviewed. Overall survival (OS) was calculated from the date of initiation of ICI to the date of death. To overcome guarantee-time bias, we calculated post-irAEs survival from the date of first irAE presentation in patients who developed irAEs or from the date of ICI initiation in pts without irAEs. Results: Primary site was the oral cavity (N = 51), oropharynx (N = 20), larynx (N = 29), hypopharynx (N = 1), paranasal sinuses (N = 5) and nasopharynx (N = 4). 41 (37.3%) had metastatic and 69 (62.7%) recurrent disease. 32 pts (29.1%) developed irAEs, with more common thyroiditis (N = 15, 13.6%). Of 100 pts with evaluable disease, 14 (14%) responded. 6/31 (19.4%) with irAEs vs. 8/69 (11.6%) without irAEs responded to ICI (p = 0.354). After a median follow-up of 16.4 months, 69 pts died. Median OS was 10 mo (95%CI, 6.7-13.4), 10 mo (95%CI, 5.6-14.5) for pts with recurrent and 10 mo (95%CI, 7.7-12.3) for pts with metastatic HNSCC (p = 0.966). Median OS was 17.9 mo (95%CI, 7.9-27.9) for pts with irAEs and 6.6 mo (95%CI, 3.3-9.9) for pts without irAEs (p = 0.001). Median post-irAEs survival was 16.3 (95%CI, 7.1-25.5) for pts with irAEs vs. 6.6 mo (95%CI, 3.3-9.9) for pts without irAEs (p = 0.020). Responders to ICI did not differ in median post-irAEs survival irrespective of whether they developed irAEs (p = 0.561), while among non-responders, those who developed irAEs had significantly longer median post-irAEs survival compared to those who did not (10 vs. 6 mo, respectively, p = 0.044). Multiviariate Cox proportional hazard models showed that independent favorable prognostic factors for post-irAEs survival were the development of irAEs (HR 0.54, 95%CI 0.30-0.97, p = 0.039) and response to ICI (HR 0.16, 95%CI 0.05-0.50, p = 0.002). Conclusions: The development of irAEs is a strong predictor of improved survival in patients with advanced HNSCC treated with ICIs.
Immune checkpoint inhibitor in nasopharyngeal carcinoma: Multi-institution experience.
Authors: Park Jong Chul , Wirth Lori J. , Clark John R , Durbeck Julia , Ho Won Jin , Boudadi Karim , Kang Hyunseok 
Published: May 2020

6538 Background: The current standard treatment for unresectable recurrent/metastatic (R/M) nasopharyngeal carcinoma (NPC) is cytotoxic chemotherapy but prognosis remains poor. Recent phase I-II trials of anti-PD-1 therapy (aPD-1) have demonstrated promising activity in R/M NPC, but the published experience is primarily limited to Epstein-Barr virus (EBV) positive tumors in the Asian population. Here we report our three institutional real-world experience with aPD-1 in patients (pts) with R/M NPC. Methods: A retrospective analysis was conducted after IRB approval at the Massachusetts General, Johns Hopkins, and University California San Francisco Hospitals. Demographic and clinical data was collected on pts with R/M NPC who received aPD-1 at the participating institutions. Objective response rate (ORR) was the primary outcome of interest and progression free survival (PFS) and overall survival were secondary outcomes. Univariate and multivariate analyses were conducted to assess association between clinicopathologic factors and outcomes, using logistic regression models. Results: A total of 36 pts were identified: 20 pts were treated with pembrolizumab and 16 with nivolumab. Median age was 50 (15-74). Twenty-nine (81%) were male. Twenty pts (56%) were Asian. Twenty-nine pts (81%) had EBV positive disease. Nine (25%) had aPD-1 as first-line therapy (1L). Molecular profiling results were available in 16 pts: TP53 mutation was the most common alteration (25%) and was limited to EBV negative tumors. Median total mutational burden (TMB) was 3/Mb (1-28). Median PD-L1 expression was 10% (0-90). Median follow up was 13.9 months (mos). Objective response was evaluable in all 36 pts: 9 pts achieved objective response (ORR 25.0%, 95% CI 12.1-42.2) with 2 complete responses: EBV positive vs. negative (27.6% vs. 14.2%, P=0.472), Asian vs. non-Asian (25% vs. 25%, P=1.000), and 1L vs. >1L (33.3% vs. 22.2%, P=0.511). Thirteen pts had stable disease (disease control rate 61.1%). Responses were seen in both TMB high (28/Mb) and low (1/Mb) tumors and no association with PD-L1 expression was observed. One-year survival rate was 81.3%. EBV positive pts had a trend towards better survival (84.8 vs. 66.7, P=0.640). Median PFS was 5.5 mos and not different between EBV positive vs. negative pts (5.6 vs. 4.0 mos, P=0.919). Conclusions: Our multi-institutional real-world experience with checkpoint inhibitor therapy in R/M NPC confirms that a similar degree of activity is seen as reported in the phase I-II experience in diverse races, but efficacy seems more prominent in EBV positive disease.
Clinical response and biomarker analysis of POLARIS-02 a phase II study of toripalimab, a humanized IgG4 mAb against programmed death-1 (PD-1) in patients with metastatic nasopharyngeal carcinoma.
Authors: Wang Fenghua , Wei Xiao-Li , Feng Jifeng , Li Qi , Xu Nong , Hu Xichun , Liao Wangjun , Jiang Yi , Lin Xiaoyan , Zhang Qingyuan , Yuan Xianglin , Huang Haixin , Chen Ye , Dai Guanghai , Shi Jianhua , Shen Lin , Yang Shujun , Shu Yongqian , Liu Yunpeng , Xu Rui-hua ,   Shanghai Junshi Biosciences
Published: May 2020

6542 Background: Metastatic nasopharyngeal cancer (mNPC) patients progressed after standard therapy have limited treatment options. This study is to evaluate the clinical efficacy and safety of toripalimab in mNPC patients refractory to standard chemotherapy treatment (Clinical trial ID: NCT02915432). Methods: Patients receive 3 mg/kg toripalimab Q2W via IV infusion until disease progression, unacceptable toxicity, or voluntary withdrawal. Clinical response is assessed every 8 weeks according to RECIST v1.1. Tumor PD-L1 expression, plasma EBV titer and other biomarkers will be evaluated for correlation with clinical response. Results: From Dec 2016 to Feb 2019, 190 mNPC patients were enrolled from 17 participating centers in China. The median age was 46 years with 83% male. Patients were heavily pretreated with a median of 2 lines of prior systemic treatments. By the cutoff date of Jan 17, 2020, 97% patients experienced treatment related adverse events (TRAE). Most common TRAE included anemia, hypothyroidism, AST increased, proteinuria and fever. Grade 3+ TRAE occurred in 28% patients. Among 190 patients assessed by Independent Review Committee per RECIST v1.1, 6 CR, 33 PR and 40 SD were observed for an ORR of 20.5% and a DCR of 41.6%. The median DOR was 12.9 months. The median PFS and median OS were 1.9 months and 18.6 months respectively. PD-L1+ patients (n=48) had higher ORR than PD-L1- patients (n=134), 27.1% versus 19.4%. By tumor histology, ORR was higher in keratinizing NPC (n=8) than non-keratinizing NPC (n=168), 62.5% versus 19.0%. 144 patients had valid plasma EBV titer measured every 28 days during the study. An average drop of 101-fold plasma EBV titer from baseline was observed in patients with objective responses. Patients with 2-fold+ drop in plasma EBV titer on day 28 (n=60) went on to have 48.3% ORR and 76.7% DCR, whereas patients with less than 2-fold drop (n=88) had 5.7% ORR and 25.0% DCR. 14 responding patients who later developed progressive disease had at least 2-fold+ increase of plasma EBV tier 3-months (median) before radiographic identification of disease progression. Conclusions: Toripalimab demonstrated encouraging clinical activity with a manageable safety profile in mNPC patients refractory to standard chemotherapy. Patients with 2-fold+ drops in plasma EBV titer on day 28 from baseline had favorable clinical response of 48.3% ORR, which might be used as a predictive biomarker. Clinical trial information: NCT02915432 .
INDUCE-1: Report on safety run-in cohorts combining Inducible T-cell co-stimulatory receptor (ICOS) agonist GSK3359609 (GSK609) with platinum+5-FU chemotherapy (5-FU/plat), with or without pembrolizumab (PE), for the treatment of advanced solid tumors.
Authors: Massarelli Erminia , Balmanoukian Ani Sarkis , Vieito Maria , Le Tourneau Christophe , Hernandez-Guerrero Tatiana , Trigo Jose Manuel , Aljumaily Raid , Chisamore Michael Jon , Rogan Debra , Sung Ruby , Henry Courtney , Turner David , Yadavilli Sapna , Franco Sonia , Ellis Catherine Elizabeth , Ballas Marc S. , Hoos Axel , Rischin Danny 
Published: May 2020

6544 Background: The KEYNOTE-048 study (Burtness, at al. Lancet 2019;394:1915–28) led to approval of PE in combination with 5-FU/plat for first-line (1L) treatment of head and neck squamous cell carcinoma (HNSCC). The Phase I INDUCE-1 study (NCT02723955) has shown that GSK609±PE has a manageable safety profile in patients (pts) with advanced solid tumors (Hansen, at al. Annals of Oncology 2018;29[suppl_8]:viii404) and that GSK609 combined with PE has anti-tumor activity in pts with anti-PD-1/L1-naïve HNSCC (Rischin, et al. Annals of Oncol 2019;30[Supplement_5]:v454–5). To evaluate the safety of GSK609±PE in combination with 5-FU/plat, we initiated additional safety cohorts. Methods: Pts eligible for GSK609+5-FU/plat had a diagnosis of advanced selected solid tumors and ≤5 prior lines of systemic therapy. Pts eligible for GSK609+PE+5-FU/plat had a diagnosis of recurrent or metastatic 1L HNSCC deemed incurable by local therapies. 5-FU/plat was administered every 3 weeks (Q3W) for 4-6 cycles (Burtness, at al. Lancet 2019;394:1915–28); GSK609 24 or 80 mg ±PE 200 mg were administered Q3W for up to 2 years/35 cycles or until disease progression or unacceptable toxicity. Results: Twenty-nine pts were enrolled in the 5-FU/plat safety cohorts: 10 pts in the GSK609+5-FU/plat cohort and 19 pts in the GSK609+PE+5-FU/plat cohort. With GSK609+5-FU/plat, 9/10 (90%) pts experienced ≥ 1 adverse event (AE). Of 32 AEs of any grade, 9 were Grade ≥3 and 3 were serious AEs (SAEs). Two of the 3 SAEs were related to study treatment (oral mucositis and febrile pancytopenia). With GSK609+PE+5-FU/plat, 18/19 (94.7%) pts experienced ≥ 1 AE. Of 119 AEs of any grade, 24 were Grade ≥3 and 15 were SAEs. Of the 15 SAEs, 11 were related to study treatment (febrile neutropenia [n=4], colitis [n=2], diarrhea [n=1], vomiting [n=1], acute kidney injury [n=1], cardiac chest pain [n=1] and lung infection [n=1]). For all cohorts, no Grade 5 AEs were observed. For 10 pts evaluable for confirmed best overall response in all cohorts, 2 pts had partial response, 6 pts had stable disease and 2 pts were nonevaluable. No difference in GSK609 exposure was observed relative to GSK609 monotherapy. Conclusions: The safety profile of GSK609 in combination with 5-FU/plat±PE is manageable. Most AEs were Grades 1 or 2 and consistent with PE and chemotherapy toxicities. Continued follow-up to investigate long-term safety and efficacy of this combination is warranted. Clinical trial information: NCT02723955 .