bluuebunny/crossref_metadata_2025_split huggingface dataset:
Health-related quality of life (HRQoL) in advanced endometrial cancer (aEC) patients (pts) treated with lenvatinib plus pembrolizumab or treatment of physician’s choice (TPC).
Authors: Lorusso Domenica , Colombo Nicoletta , Casado Herraez Antonio , Santin Alessandro , Colomba Emeline , Miller David Scott , Fujiwara Keiichi , Pignata Sandro , Baron-Hay Sally E. , Ray-Coquard Isabelle Laure , Shapira-Frommer Ronnie , Kim Yong Man , McCormack Mary , Bird Steven , Prabhu Vimalanand S. , Martin Nguyen Allison , Zhao Qi , Dutta Lea , Makker Vicky 
Published: June 2021

5570 Background: In Study 309/KEYNOTE-775, lenvatinib + pembrolizumab (L+P) demonstrated significant and clinically meaningful improvement in OS, PFS, and ORR compared with TPC in aEC pts following prior platinum-based systemic therapy. Given the medical complexity/age of EC pts, QoL analyses are critical, but often under-reported. We present results of pt-reported HRQoL for Study 309/KEYNOTE-775. Methods: Pts were randomized 1:1 to receive lenvatinib 20 mg QD PO + pembrolizumab 200 mg IV Q3W (n=411) or TPC (n=416; doxorubicin 60 mg/m2 IV Q3W or paclitaxel 80 mg/m2 IV QW, 3 wks on/1 wk off). Pt-reported HRQoL was assessed at cycle 1 day 1, day 1 of each subsequent cycle and at time of discontinuation using EORTC QLQ-C30, its EC module QLQ-EN24, and EQ-5D-5L in treated pts who had ≥1 HRQoL assessment available. Higher scores indicate better functioning/QoL (EORTC QLQ-C30, EQ-5D-5L) or worse symptom severity (QLQ-EN24). Changes in EORTC QLQ-C30 global health status (GHS)/QoL was a secondary endpoint. This was analyzed from baseline to the latest timepoint at which overall completion was ≥60% and overall compliance was ≥80%, using constrained longitudinal data analysis; other HRQoL analyses were exploratory. Results: Completion and compliance rates of EORTC QLQ-C30 were >95% in both groups at baseline. Primary analysis was conducted at wk 12 as completion rate was 80% for L+P and 62% for TPC; compliance rate was 93% for L+P and 87% for TPC. Baseline GHS/QoL scores were similar between the L+P group and TPC group: mean (SD) of 65.74 (21.87) vs 65.69 (22.71), respectively. Over 12 wks of follow-up, pts in both groups had slight decreases in GHS/QoL. Similar decreases were observed for pts receiving L+P vs TPC: -5.97 (95% CI: -8.36, -3.58) vs -6.98 (95% CI: -9.63, -4.33). The between-group difference in least-squares (LS) mean score change from baseline to wk 12 for L+P vs TPC was 1.01 points (95% CI: -2.28, 4.31). Over time, QoL scores were generally similar across treatments. Results were similar for other HRQoL endpoints (Table). Conclusions: No significant differences were observed in HRQoL scores between treatment groups. With no standard treatment approach following failure of platinum-based therapy, these data along with previously reported efficacy and safety findings from Study 309/KEYNOTE-775 further support that L+P has an overall favorable benefit/risk profile compared to chemotherapy. Clinical trial information: NCT03517449. [Table: see text]
Race-related disparities in patterns of uterine cancer recurrence.
Authors: Dagum Camilla , Vilardo Nicole , Gressel Gregory M. 
Published: June 2021

5571 Background: Racial disparities in uterine cancer outcomes are present, as Black patients with uterine cancer have markedly higher mortality when compared with White patients. Potential etiologies of this discrepancy have been investigated, including implicit bias, histopathologic factors and stage at presentation, molecular and genetic factors, and socioeconomic factors. The purpose of this study is to explore if non-White patients with uterine cancer are more likely to experience distant cancer recurrence compared to White patients. Methods: A single-institution retrospective cohort study was performed examining all patients diagnosed with uterine cancer from 2006-2016. Data regarding patient demographics, medical co-morbidities, histology, stage, treatment course, and disease recurrence were abstracted from the medical record. Race was categorized based on how a patient was registered in the medical record. The primary outcome was location of recurrence, with local recurrence defined as vaginal/cuff recurrence and distant recurrence representing nodal, intraperitoneal, or distant recurrence. A multivariable regression model was built in a backwards stepwise fashion to examine the association of individual covariates with distant recurrence as opposed to vaginal recurrence. Results: A total of 1205 patients with uterine cancer were included for analysis. Three hundred eighteen (26.5%) patients were White, 472 (39.2%) Black, 319 (26.5%) Hispanic, 91 (7.6%) Asian, and 4 (0.3%) other. A total of 223 (18.5%) patients experienced disease recurrence. Black women experienced a statistically significant increased risk of recurrence compared with non-Black women [OR 1.99 (95% CI 1.37-2.88), p < 0.01]. Additionally, Black patients were significantly more likely to experience nodal, intra-peritoneal and distant recurrences relative to White patients (p < 0.01). When adjusting for covariates including race, histology, grade, stage and adjuvant treatment, non-White race [OR 3.87 (95% CI (1.42-10.54), p < 0.01] was associated with significant increase in risk of distal recurrence. Conclusions: The findings of this study suggest that non-White race is potentially contributory to distant recurrence of uterine cancer, even when accounting for histopathologic differences, stage at presentation, and other traditional covariates. These findings suggest that the disparate outcomes experienced by non-White patients are likely multi-factorial in nature and highlight the need for efforts focused on optimizing treatment and improving outcomes of non-White women with uterine cancer.[Table: see text]
Evaluating the role of aromatase inhibitors (AIs) in the treatment of endometrial stromal sarcomas (ESS).
Authors: Crowley Fionnuala , Cadoo Karen Anne , Chiang Sarah , Mueller Jennifer Jean , Hensley Martee Leigh , O'Cearbhaill Roisin Eilish 
Published: June 2021

5575 Background: Endometrial stromal sarcomas (ESS) account for < 20% of uterine sarcomas. They usually express estrogen and progesterone receptors (ER/PR) and are considered hormone sensitive. Due to the rarity of these tumors, large clinical trials studying optimal treatment have not been possible. This study represents the largest retrospective study of ESS treated with AI. Methods: The clinicopathological variables and outcomes of patients (pts) with pathologically confirmed low grade ESS treated with AI at our institution between 1998-2020 were recorded. Results: 48 pts with ESS treated with AI were identified. They had a median age of 54 years (range 23-84) and BMI of 27 (range 20-50). 79% were white. 6 (12%), 9 (19%), 14 (29%) and 19 pts (40%) had stage 1,2,3,4 ESS, respectively. 37 (77%) were ER+/PR+; 2 (4%) ER+/PR- and 9 pts (19%) had unknown ER/PR status. All pts were postmenopausal at AI initiation. 12 pts (25%) had a synchronous cancer (5 of these had breast cancer {3 of the 5 presented post tamoxifen}). 23 pts (48%) received megestrol acetate and 25 (52%) an AI as first line hormonal manipulation. During their disease course, 35 pts (73%) received letrozole, 21 (44%) anastrozole and 19 (39.6%) exemestane. 22 pts (46%) were treated with more than one AI. 28 pts (58%) reported side-effects; arthralgia (33%) being the most common. 10 pts (21%) discontinued AI due to toxicity; 12 pts (25%) switched AI for toxicity (with improved tolerance in 67% of these pts). Among the 24 pts (50%) with measurable disease there were 2 partial responses (objective response rate of 8.3%). 1-year disease control rate (DCR) was (79%) for all pts and 58% in stage 4 disease. Median PFS for 1st line AI was 161.6 months (95% CI 48.5 to 274.7). Conclusions: This study represents the largest study of AI use in ESS to date. We found the ORR to be more modest than previously reported. The majority of pts had prolonged stable disease with a DCR of 58% even in stage 4 disease. Pts who progress on one AI may benefit from trial of a 2nd AI. A phase 2 study of interruption versus maintenance AI in locally advanced/metastatic ESS is currently underway (NCT03624244).
Multi-gene prognostic assays and age-related differences in prediction of pathologic complete response to neoadjuvant chemotherapy and survival in breast cancer.
Authors: Hanson Kent , Hoskins Kent , Ko Naomi Yu , Calip Gregory Sampang 
Published: June 2021

591 Background: Multi-gene testing of primary breast tumors in early-stage breast cancer is used to classify the risk of developing distant metastases and predict the benefit of adjuvant chemotherapy. The association between the tumor genomic prognostic score (GPS) and response to neoadjuvant chemotherapy (NACT) and survival is not well characterized. Our objective was to describe the association between GPS and rates of pathologic complete response (PCR) and subsequent overall survival among women with or without PCR. Methods: We utilized the National Cancer Database to perform a hospital-based, retrospective cohort study of breast cancer patients ages 18 years and older. We included women diagnosed with first primary stages I-III hormone receptor positive (HR+), HER2 negative (HER2-) breast cancer who received NACT and surgery between 2010 and 2017. Women were categorized as having low (0-10 or 200), intermediate (11-25 or 300), or high-risk (25-199 or 400) GPS based on OncotypeDX or MammaPrint scores. Multivariable modified Poisson regression models with robust error variance were used to estimate the crude and adjusted relative risk and 95% confidence intervals (CI) for PCR associated with GPS groups. Multivariable Cox proportional hazards models were used to estimate adjusted hazard ratios (HR) and 95% CI for associations between the GPS and overall survival (OS) in women who did and did not have PCR. Results: A cohort of 3,446 women (mean [SD] age, 56.7 [12.0] years; median [interquartile range] follow-up of 47 [31-68] months) who received genomic testing and neoadjuvant chemotherapy were included in our analysis, of which 935 (27%) were low risk, 1,357 (39%) intermediate risk, and 1,154 (34%) high risk GPS. The relative risk of PCR for all women with high GPS was 1.81 (95% CI, 1.47-2.22; p < 0.001) in crude models and 1.49 (95% CI, 1.16-1.92; p = 0.002) after full adjustment compared to low GPS. Across all models, having a high GPS was significantly associated with achieving PCR in younger women ( < 65 years). In women ages ≥65 years, the association between GPS and PCR was not predictive nor statistically significantly. Among women with no response or partial response to NACT, high GPS was associated with a significantly increased risk of overall mortality (HR 2.41; 95% CI, 1.61-3.60; p < 0.001) compared to low GPS. Conversely, in women who did achieve PCR, GPS was not predictive of overall mortality across all age groups. Conclusions: In women with HR+/HER2- breast cancer, high risk GPS was predictive of PCR following NACT, primarily in younger women ( < 65 years). Our findings also indicated GPS was associated with lower OS in high-risk patients who do not achieve PCR and unpredictive of OS in those without PCR. The utility of tumor genomic testing in the neoadjuvant setting needs further investigation.
Metronomic capecitabine as adjuvant therapy in locoregionally advanced nasopharyngeal carcinoma: A phase 3, multicenter, randomized controlled trial.
Authors: Ma Jun , Chen Yu-Pei , Sun Ying , Zhou Qin , Yang Kun-Yu , Jin Feng , Zhu Xiao-Dong , Shi Mei , Hu Guoqing , Sun Yan , Wu Hong-Fen , Wu Hui , Lin Qin , Wang Hui , Tian Ye , Zhang Ning , Wang Xicheng , Shen Liangfang , Xie Fangyun , Liu Xu 
Published: June 2021

6003 Background: Patients suffering from locoregionally advanced nasopharyngeal carcinoma (NPC) commonly develop disease recurrence, despite a high rate of complete clinical remission after standard of care (concurrent cisplatin-radiotherapy, with or without induction chemotherapy). The benefit of additional adjuvant chemotherapy remains unclear. Methods: Patients with high-risk locoregionally advanced NPC (stage III to IVA, excluding T3-4N0 and T3N1), and with no locoregional disease or distant metastasis after definitive chemoradiotherapy, were eligible. They were randomly assigned (1:1) within 12 to 16 weeks after the last radiation dose to receive either capecitabine at a dose of 650 mg/m2 twice daily for 1 year (metronomic capecitabine group) or observation (standard-therapy group). The primary end point was recurrence-free survival (RFS). The calculated sample size was 201 per group, with an 80% power (two-sided α 0.05) to detect a target hazard ratio (HR) of 0.52. Results: A total of 406 patients underwent randomization, comprising 204 in the metronomic capecitabine group and 202 in the standard-therapy group. After a median follow-up of 36 months (corresponding to 43 months when calculated from the start of standard therapy), the estimated 3-year RFS was 85.9% in the metronomic capecitabine group, as compared with 76.5% in the standard-therapy group (intention-to-treat population; HR 0.51, 95% confidence interval 0.32–0.81; P = 0.003). The incidence of grade 3 adverse events was 17.4% in the metronomic capecitabine group and 5.5% in the standard-therapy group; hand-foot syndrome was the most common adverse event related to capecitabine (9.0%). One grade 4 neutropenia occurred in the metronomic capecitabine group. Neither group sufferd from treatment-related deaths. During treatment, there was no clinically meaningful deterioration of health-related quality of life associated with the use of metronomic adjuvant capecitabine. Conclusions: The addition of metronomic capecitabine as adjuvant therapy to chemoradiotherapy significantly improved RFS in locoregionally advanced NPC, with a manageable safety profile and no compromise to quality of life. Clinical trial information: NCT02958111. [Table: see text]
Toripalimab plus intensity-modulated radiotherapy for recurrent nasopharyngeal carcinoma: An open-label single-arm, phase II trial.
Authors: Chen Mingyuan , Hua Yijun , You Rui , Wang Zhi-Qiang , Huang Peiyu , Lin Mei , Ouyang Yan-Feng 
Published: June 2021

6023 Background: Toripalimab is a humanized immunoglobulin G4 monoclonal antibody against programmed death 1 (PD-1). We aimed to investigate the efficacy and safety of toripalimab in combination with intensity-modulated radiotherapy (IMRT) for recurrent nasopharyngeal carcinoma (rNPC). Methods: We conducted a single-arm, phase II trial with rNPC patients who had biopsy-proven disease and were unsuitable for local surgery. Eligible patients received IMRT in combination with toripalimab administered via intravenous infusion of 240 mg once every 3 weeks for a maximum of seven cycles. The primary endpoint was the objective response rate (ORR). The secondary endpoints included safety profiles, progression-free survival (PFS). Results: Between May 2019 and January 2020, a total of 25 rNPC patients were enrolled (18 men [72.0%] and 7 women [28.0%]; median [IQR] age, 49.0 [43.5-52.5] years). With a median (IQR) follow-up duration of 14.6 months (13.1-16.2) months, 19 patients (79.2%) achieved an overall response, and disease control was achieved in 23 (95.8%) patients at 3 months post radiotherapy. The 12-month progression-free survival was 91.8% (95% CI 91.7% - 91.9%). The incidences of acute (grade ≥3) blood triglyceride elevation, creatine phosphokinase elevation, skin reaction, and mucositis were 1 (4.0%), 1 (4.0%), 2 (8.0%), and 1 (4.0%), respectively. The incidences of late severe (grade ≥3) nasopharyngeal wall necrosis, nasal bleeding, and trismus were 28.0%, 12.0%, and 4.0%, respectively. Conclusions: Toripalimab combined with IMRT was tolerable and showed promising antitumor activity in rNPC patients. Clinical trial information: NCT03854838.
Results from a phase II study of eftilagimod alpha (soluble LAG-3 protein) and pembrolizumab in patients with PD-L1 unselected metastatic second-line squamous head and neck carcinoma.
Authors: Brana Irene , Forster Martin , Lopez-Pousa Antonio , Doger Bernard , Roxburgh Patricia , Bajaj Pawan , Urueta Portillo Daniela , Quiroga Vanesa , Krebs Matthew , Mueller Christian , Triebel Frederic 
Published: June 2021

6028 Background: Eftilagimod alpha (efti) is a soluble LAG-3 protein that binds to a subset of MHC class II molecules to mediate antigen presenting cell (APC) activation and CD8 T-cell activation. The stimulation of the dendritic cell network and subsequent T cell recruitment with efti may lead to stronger anti-tumor responses in combination than observed with pembrolizumab alone. We hereby report results of the 2nd line metastatic squamous head and neck carcinoma (HNSCC) cohort (part C) of phase II trial (NCT03625323). Methods: Patients (pts) with HNSCC progressed on or after 1st line platinum-based therapy and unselected for PD-L1 expression were recruited into part C. The study used a Simon's 2-stage design (18 pts planned for stage 1 and 19 for stage 2), with objective response rate (ORR) by iRECIST as the primary endpoint (EP). Secondary EPs include tolerability, disease control rate (DCR), progression free survival (PFS), overall survival (OS), pharmacokinetics, pharmacodynamics and immunogenicity. Efti was administered as 30 mg subcutaneous injection every 2 wks for 8 cycles and then every 3 wks for 9 cycles with pembrolizumab (200 mg intravenous infusion every 3 wks for up to 2 yrs). Imaging was performed every 8 weeks. PD-L1 was assessed centrally (22C3 clone). The study was approved by ethics committees and institutional review boards. Results: In total 38 pts were enrolled. The median age was 62 yrs (range 37-84) and 89 % were male. The ECOG PS was 0 and 1 in 34% and 66%, respectively. Primary location at diagnosis was the oral cavity (29%), oropharynx (37%), hypopharynx (18%) and the larynx (16%). All PD-L1 subgroups (CPS < 1 %, ≥ 1 to ≤19; ≥20) were included. All pts were pre-treated with platinum-based chemotherapy. Pts received a median of 3.0 (range 1 – 21) pembrolizumab and 5.0 (range 1-31) efti administrations. Thirty-five (35) pts were evaluated for response (cut-off Jan 2021) with 4 (11 %) pts showing CR, 7 (20 %) pts PR, 3 (9 %) pts SD, 16 (46 %) pts PD with 5 (14 %) pts being not evaluable as per iRECIST. ORR was reported with 31.4 % (95 % CI 16.9 % - 49.3 %) and DCR 40 %Median PFS was 2.1 months and 35 % were progression free at 6 months. Median OS (46 % events) was 12.6 months. There were no adverse reactions leading to treatment discontinuation. The most common ( > 10 %) treatment emergent adverse events were cough (18 %), asthenia (16 %), dyspnea (11 %), fatigue (13 %), diarrhea (11 %), hypothyroidism (11%), upper respiratory tract infection (11%) and back pain (11%). Conclusions: Efti in combination with pembrolizumab is safe and shows encouraging antitumor activity in platinum pre-treated 2nd line HNSCC patients. Clinical trial information: NCT03625323.
A phase III multicenter randomized clinical trial to compare cisplatin plus fluorouracil with or without docetaxel as the first-line induction chemotherapy for locoregionally advanced nasopharyngeal carcinoma: Long-term outcomes update.
Authors: FangZheng Wang Fang 
Published: June 2021

6032 Background: A phase III multicenter prospective randomized controlled trial was conducted to compare cisplatin plus 5-fluorourcil with or without docetaxel as first-line induction chemotherapy in the patients with locoregionally advanced nasopharyngeal carcinoma (LANPC). Here, we report on the long-term outcomes and late toxicities of the trial (NCT01536223). Methods: Patients with newly diagnosed LANPC, stage III-IV disease, Karnofsky performance score≥70, without metastasis were eligible and randomly assigned 1:1 to TPF versus PF for three cycles. The primary end point was progression-free survival; local control, OS and advent events were important key secondary end points. The Kaplan-Meier method and the log-rank test were used to conduct and compare the survival curves in this study. Results: Two hundred ninety-nine patients were enrolled. 276 patients (138 TPF and 138 PF) were evaluable. Baseline characteristics were well-balanced between two groups, and the median age was 48 (range, 18-60 years). The ORR rates after induction chemotherapy and chemoradiotherapy were 90.6% and 9797.8% in TPF group and 87.0% (P > 0.05) and 97.8% (P > 0.05), respectively. The median follow-up was 99 months. For all patients, the 5- and 8-year OS and PFS were 76.9% and 74.9%, 72.3% and 69.1%, respectively. PF was associated with a similar PFS versus TPF ( 5-year PFS of 72.4% versus 73.2%, P =.747), and an equivalent OS at 5 years ( 79.2% and 79.1%, P = 0.519). Treatment-related grade 3 to 4 advent events were less frequent with PF compared with TPF. Conclusions: With prolonged follow-up, the survival outcomes in the PF group were not non-inferiority to those in the TPF group, but grade 3 to 4 advent events were less frequent. Clinical trial information: NCT01536223.
Adjuvant toripalimab or combined with S-1 in recurrent, previously irradiated head and neck squamous cell carcinoma treated with salvage surgery: A phase II clinical trial (The RePASS study).
Authors: Dou Shengjin , Li Rongrong , Zhang Lin , Jiang Wen , Ye Lulu , Zhu Guopei 
Published: June 2021

6039 Background: The predominant pattern of failure for Head and Neck Squamous Cell Carcinoma (HNSCC) is locoregional disease. Salvage surgery remains the standard of care for operable disease. Re-irradiation after previous full course radiotherapy generally has been considered contraindicated. Since anti-PD-1 antibodies were efficacious and safety in recurrent/metastatic HNSCC, this study aimed to evaluate the efficacy and safety of adjuvant toripalimab (anti-PD-1 antibody) in recurrent, previously irradiated HNSCC treated with salvage surgery. Methods: This study was a single-arm, phase II study. Patients with HNSCC occurring in an area of previously irradiated and with at least one high risk factors after salvage surgery (1- positive margin; 2- extranodal extension; 3- rStaging T3-4/N2-3/T2N1) were enrolled. In the Stage I of 12 patients, patients received toripalimab 240mg once every 3 weeks until confirmed disease progression or unacceptable toxicity, for 12 months. In the stage II of 8 patients with PD-L1 CPS≥1, patients received toripalimab combined with S-1, which was given orally at 25 mg/m2, twice daily, on day 1 to 14, repeated every 21 days for 4-6 cycles. The primary endpoint was 1-year progression-free survival (PFS). We hypothesized a 1-year PFS of at least 56% and assumed a null hypothesis of 34%. A retrospective cohort of 16 patients was compared. Results: Between May 2019 and December 2020, 20 patients were enrolled. High-risk factors included ENE (35%), positive margin (25%), T3-4(30%) and T2N+(10%). Seventeen patients have PD-L1 CPS≥1 and 3 patients have CPS＜1. With a median follow-up of 11.2 months, estimated 1-year PFS and overall survival was 57.0% (95% confidence interval, 32%– 77%) and 79.2% (51%–91%). The primary PFS endpoint has exceeded the hypothesis and its median has not been reached. When compared to the retrospective cohort, the PFS was significantly better(p=0.001)，even for Stage I patients(Median PFS: 5.1 vs 3.7 months, p=0.03 ). Stage II patients resulted a better PFS and OS compare to stage I (p=0.02 and p=0.002). For patients with CPS≥1, 1-year PFS and OS was 79.1% (95% confidence interval, 51%–91%) and 91.7%(68%–99%), which were significantly better than patients with CPS＜1 (p=0.001 and p=0.05). Adjuvant Toripalimab or combine with S-1 was well-tolerated with no grade 3-4 toxicity and dose interruption as a result of treatment-related adverse event only occurred in 2 patients. Flow cytometry revealed that patients with short PFS had fewer baseline overall count of B cells(p=0.09). Conclusions: Adjuvant Toripalimab or combined with S-1 after salvage surgery is efficacious and safety in recurrent, previously irradiated HNSCC, and a better PFS was observed in patients treated with combined therapy and with CPS≥1. Further randomized trials are warranted. Clinical trial information: NCT04126460.