bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nivolumab as second-line treatment and beyond for metastatic renal cell carcinoma: A real-life experience from Turkish Oncology Group Kidney Cancer Consortium (TKCC) Database.
Authors: Yekeduz Emre , Erturk Ismail , Tural Deniz , Karadurmus Nuri , Karakaya Serdar , Hizal Mutlu , Arslan Çağatay , Taban Hakan , Küçükarda Ahmet , Şentürk Öztaş Nihan , Sever Ozlem Nuray , Uçar Gokhan , Sendur Mehmet Ali Nahit , Demirci Umut , Kilickap Saadettin , Cicin Irfan , Oksuzoglu Berna , Ozguroglu Mustafa , Urun Yuksel ,   Turkish Oncology Group Kidney Cancer Consortium (TKCC)
Published: March 2021

321 Background: Immune checkpoint inhibitors (ICIs) started a new era in the treatment of metastatic renal cell carcinoma (mRCC). CheckMate-025 and CheckMate-214 trials established the effect of ICIs in the second-line and upfront therapy of mRCC, respectively. This study aimed to share a real-life experience regarding nivolumab in the second-line treatment and beyond in mRCC Methods: We retrospectively searched the Turkish Oncology Group Kidney Cancer Consortium (TKCC) database, which is the multicenter registry system, and extracted patients treated with nivolumab in the second line and beyond. The patients treated with nivolumab plus targeted therapy or ipilimumab were excluded. The primary endpoint was overall survival (OS). The secondary endpoints were response rates and safety. Results: A total of 134 patients were included in this study. The median age at the starting of nivolumab treatment was 61 years (Inter Quartile Range (IQR):55-67). Three out of four patients were male. One hundred four patients (78%) had previous nephrectomy. The majority of patients had clear-cell pathology (83%). Thirteen patients (10%) had sarcomatoid features. According to International Metastatic RCC Database Consortium (IMDC) risk score, seventy patients (52%) were in the intermediate and poor prognostic group. The previous drugs administered in each line before nivolumab are shown in the table below. The number of patients treated with nivolumab was 63(47%), 45(33%), 17(13%), and 9(7%) in the second-, third-, fourth-, and fifth-line setting, respectively. The median OS was 34 months (95% Confidence Interval (CI): 24.1-43.8)) with the 15 months (IQR:5-26) median follow-up. Objective response rate (ORR) and disease control rate (DCR) was 33% and 57%, respectively. The most common grade 3 or higher AEs leading to treatment discontinuation were pneumonitis (%1.4) and colitis (<%1). Conclusions: In compliance with the CheckMate-025 trial results, nivolumab improved OS for mRCC patients treated in the second line and beyond. The median OS was slightly higher in our study than the CheckMate-025 (34 months versus 25.8 months). It may be associated with the patient population in our study. Patients up to the fifth-line setting of mRCC treatment were included in this study. Of note, there was no additional safety concern for nivolumab. [Table: see text]
UNISON - nivolumab then ipilimumab + nivolumab in advanced non-clear cell renal cell carcinoma (ANZUP 1602): Part 1—Nivolumab monotherapy.
Authors: Gedye Craig , Pook David William , Krieger Laurence Eliot Miles , Harris Carole A. , Goh Jeffrey C. , Kichenadasse Ganessan , Gurney Howard , Underhill Craig , Parnis Francis , Joshua Anthony M. , Ferguson Tom , Roncolato Felicia , Harrison Michelle L. , Begbie Stephen , Morris Michelle Frances , Hovey Elizabeth J. , George Mathew , Prithviraj Prashanth , Liow Elizabeth Chien Hern , Davis Ian D. ,   ANZUP Cancer Trials Group
Published: March 2021

325 Background: Immune checkpoint inhibitors (ICI) are active in many cancers, but people with rare variant, non clear-cell renal cell carcinoma (nccRCC) have been excluded from most clinical trials in RCC. UNISON (NCT03177239) aimed to test 2 hypotheses; the activity of nivolumab in nccRCC (Part 1), and the benefit of adding ipilimumab to nivolumab, in people whose cancers progress on nivolumab (Part 2). Methods: 83 participants (pts) with advanced nccRCC with good (ECOG0/1) performance status, were enrolled including papillary type 1 (17%), papillary type 2 (28%), chromophobe (18%), Xp11 translocation (6%), hereditary leiomyomatosis renal cell carcinoma syndrome-associated renal cell carcinoma (6%), RCC unclassified (10%) and other (15%) histological subtypes. Participants took nivolumab (N) 240mg every two weeks in Part 1 in total. If they experienced progression and remained eligible they could take N (3mg/kg) plus ipilimumab (I; 1mg/kg) every 3 weeks for up to 4 doses (Part 2). Pts with disease control after N or N + I could continue N for up to 1 year. UNISON was powered to distinguish a clinically-relevant improvement in objective tumor response rate (OTRR) from 15% to 30% in people taking N+I in Part 2 in pts whose cancers were refractory to single-agent first-line N. Here we report results of Part 1. Results: Pts experience of N appeared similar to previous reports, with most experiencing mild adverse events. 12 treatment related SAE occurred in 11 patients (13%). 14 pts (17%) experienced treatment delays, or permanent treatment discontinuation (10%). The median time on treatment was 5.1 months. The OTRR was 17% with 3 complete responses and 11 partial responses. The median duration of response was 21 months. Stable disease occurred in 49% of pts and disease progression in 34%. The disease control rate at 6 months was 45% (95% CI: 34%, 56%). The median PFS was 4.0 months (95% CI: 3.6, 7.4). The 6 month progression-free survival (PFS) was 45% (95% CI: 34-55) and the 12 months PFS was 30% (95% CI: 21%, 40%). Conclusions: Pts with nccRCC treated with N experience similar adverse events compared to pts with other cancers. A substantial minority of people with nccRCC derive benefit, but many pts have cancers refractory to anti-PD1, similar to other reports. The activity of I and N in this PD1-refractory population is of considerable interest and will be reported at a later date. Clinical trial information: NCT03177239 .
Change in neutrophil to lymphocyte ratio (NLR) as a predictor of treatment failure in renal cell carcinoma patients: Analysis of the IROC (Investigating RCC Outcomes) cohort.
Authors: Basu Arnab , Phone Audrey , Bice Tristan , Sweeney Patrick , Acharya Luna , Suri Yash , Chan Abigail Sy , Nandagopal Lakshminarayanan , Garje Rohan , Zakharia Yousef , Kilari Deepak , Koshkin Vadim S , De Shazo Mollie R. , Barata Pedro C. , Desai Arpita 
Published: March 2021

344 Background: IROC is an expanding multi-institution collaborative database which includes socioeconomic, genomic, pathologic, clinical and laboratory data in metastatic RCC patients (pts), primarily in the modern setting. Elevated baseline NLR is now an established poor prognostic factor in renal cell carcinoma (RCC) but currently has limited practical use. We hypothesized that an increase in NLR of 3 or more (NLR Failure) at 2 months on therapy could be a predictor of eventual treatment failure and shorter overall survival and thus augment the utility of this marker. Methods: Patients with complete data on NLR at time = 0 and +2 months of therapy were analyzed. Information on comorbidities, previous therapy, demographics were collected for adjusted analysis. NLR failure was defined as an increase of 3 or more compared to baseline NLR. Cox proportional hazard models were used to analyze the risk of progression and death with NLR failure at 2 months (+/- 2 weeks). Kaplan Meier graphs were constructed to trace survival functions for PFS and OS by NLR. Results: Among 165 pts; 121 were eligible (Table). NLR failure at 2 months was associated with a highly statistically significant increase in the risk of death in < 1 year (HR 6.82, 95% CI [3.16-14.70], p<0.001). In a model adjusted for NLR change, the value of baseline NLR to predict OS <1 year was non-significant (HR 1.02, p = 0.65). Similarly, NLR failure increased the risk of treatment failure in less than 6 months (HR 4.83 95% CI [ 2.29-10 .19], p<0.001), while baseline NLR did not predict it (HR 1.03, p = 0.34). These findings were unaffected by immunotherapy vs TKI therapy. NLR failure at 2 months had a 78% (11/14) positive predictive value for survival <1 year and 86% (12/14) [p=.0001] for treatment failure in 6 months. Conclusions: In this multi-institutional cohort of RCC pts; an increase in NLR of 3 or more at 2 months following therapy start predicts for an increasing risk of death and impending treatment failure with a high PPV. The prognostic value of baseline NLR is non-significant when adjusting for NLR change. NLR failure should be validated in prospective studies and could have clinical utility in management of RCC pts. [Table: see text]
Prediction model for brain metastasis (BM) in patients with metastatic germ-cell tumors (mGCT) accounting for size of pulmonary metastases.
Authors: Ashkar Ryan , Althouse Sandra K. , Cary Clint , Masterson Timothy A. , Foster Richard , Hanna Nasser H. , Einhorn Lawrence H. , Adra Nabil 
Published: March 2021

378 Background: BM is an independent adverse prognostic factor that can lead to treatment complications and failure in pts with mGCT. We aimed to establish an effective and practical BM prediction model accounting for size of pulmonary metastases. Methods: 2,291 consecutive pts with mGCT treated at Indiana University between January 1990 and September 2017 were identified. Pts were divided into 2 categories: BM present (N=154) and BM absent (N=2137). Kaplan-Meier methods were used to analyze progression free survival (PFS) and overall survival (OS). Logistic regression was used to determine a predictive model for whether BM was present. The data was separated 50/50 into training and validation datasets with equal numbers of events in each. Size of pulmonary metastases were calculated based on the sum of long axis diameter of pulmonary metastases for each patient and were divided into <3cm vs. ≥3cm. Results: Baseline characteristics for 2 groups are listed in the table below. 2-yr PFS and OS for pts with vs without BM: 17% vs 65% (p<0.001) and 62% vs 91% (p<0.001) respectively. Among the 154 pts with BM, 64 (42%) had radiation only (whole-brain radiotherapy or gamma knife), 22 (14%) had BM-surgery only, 14 (9%) had both radiation and BM-surgery. 54 pts (35%) did not receive local therapy for BM. A stepwise selection was used to determine the best model with p<0.15 as the entry and staying criteria. The model with the largest ROC AUC was used moving forward. The model was tested in the validation dataset. A model was generated including age at diagnosis≥40 (1 point), pre-chemotherapy hCG≥5000 (1 point), presence of bone metastases (1 point), choriocarcinoma predominant histology (2 points), and presence of pulmonary metastases size <3 cm (2 points) or ≥3 cm (3 points). Patients with 0 points had a 0.6% probability of having BM, 1 point → 1.4%, 2 points → 3.5%, 3 points → 8.2%, 4 points → 18.3%, 5 points → 36%, 6 points → 58%, 7 points → 78%, and 8 points → 90%. Conclusions: The prediction model developed in this study demonstrated discrimination capability of predicting BM occurrence in mGCT and can be used by clinicians to identify high-risk pts. [Table: see text]
Management of fibroblast growth factor receptor inhibitor (FGFRi) treatment-emergent adverse events (TEAEs) of interest in patients (Pts) with locally advanced or metastatic urothelial carcinoma (mUC).
Authors: Siefker-Radtke Arlene O. , Necchi Andrea , Park Se Hoon , García-Donas Jesús , Huddart Robert A , Burgess Earle F , Fleming Mark T. , Rezazadeh Arash , Mellado Begona , Varlamov Sergei , Joshi Monika , Duran Ignacio , Tagawa Scott T. , Zakharia Yousef , Qi Keqin , Monga Manish , Sondhi Manu , OHagan Anne , Loriot Yohann 
Published: March 2021

426 Background: Erdafitinib (ERDA), a pan-FGFR kinase inhibitor, was US FDA approved for adults with mUC with susceptible FGFR3/2 alterations ( FGFRa) who progressed on ≥ 1 line of prior platinum-based chemotherapy based on primary results of the BLC2001 trial (NCT02365597). At final analysis (median 2-y follow-up), ERDA showed median OS of 11.3 mo and a manageable safety profile. Some FGFRi toxicities are distinct from those of other small-molecule TKIs. Proactive AE management can avoid treatment discontinuation, ensuring maximum benefit. We report the frequency and management of TEAEs of interest (central serous retinopathy [CSR], hyperphosphatemia [“on-target” FGFRi class effect], stomatitis, and skin and nail toxicities) for the optimal schedule of ERDA from the final analysis of BLC2001. Methods: The open-label, phase II BLC2001 study enrolled pts with measurable mUC, prespecified FGFRa, and progression during/after ≥ 1 line of prior chemotherapy or ≤ 12 mos of (neo)adjuvant chemotherapy or who were cisplatin ineligible, chemo naive. Optimal dose schedule in the study was 8 mg/d continuous ERDA in 28-d cycles with uptitration to 9 mg/d (ERDA 8 mg/d UpT) if prespecified serum phosphate level was not reached and no significant TEAEs occurred. ERDA 8 mg/d UpT safety results as of Aug 9, 2019 (final analysis) are summarized here. AEs were graded using NCI CTCAE v4.0. Results: Median follow-up for 101 pts treated with ERDA 8 mg/d UpT was 24.0 mos; median treatment duration was 5.4 mos. All pts had ≥ 1 TEAE. Hyperphosphatemia, stomatitis, nail disorders, skin disorders, and CSR TEAEs occurred in 78%, 59%, 59%, 55%, and 27% of pts, respectively (few were grade [gr] 3; none were gr ≥ 4; Table). TEAEs were mostly managed with concomitant treatment and dose modifications. As of data cutoff, hyperphosphatemia had resolved in 74/79 (94%) pts; stomatitis in 44/60 (73%); nail and skin TEAEs in 26/60 (43%) and 25/55 (45%), respectively; and CSR in 17/27 (63%). Most unresolved TEAEs were gr 1–2. No treatment-related deaths occurred. Conclusions: ERDA had measurable benefit in pts with advanced UC with FGFRa. As with other targeted therapies, exposure to ERDA is associated with a pattern of AEs. The most common and FGFRi class effect TEAEs were generally reversible and managed by supportive care and dose modification. Clinical trial information: NCT02365597 . Research Sponsor: Janssen Research & Development, LLC[Table: see text]
Preliminary analysis of a phase II, multicenter, randomized, active-control study to evaluate the efficacy and safety of eganelisib (IPI 549) in combination with nivolumab compared to nivolumab monotherapy in patients with advanced urothelial carcinoma.
Authors: Tomczak Piotr , Popovic Lazar , Barthelemy Philippe , Janicic Aleksander , Sevillano Fernandez Elena , Borchiellini Delphine , Aglietta Massimo , Maroto José , Carnot Aurelien , O'Connell Brenda , ZIZLSPERGER NORA , Zhang Halle Huihong , Valderrama Begoña P. 
Published: March 2021

436 Background: Inhibition of the PD-1 pathway has demonstrated clinical benefit in metastatic urothelial carcinoma (mUC); however, response rates of 15% to 29% highlight the need for more effective therapies, especially for PD-L1- patients. Eganelisib is a first-in-class, novel, oral agent which selectively inhibits PI3K-γ, with the goal of improving the immune response to checkpoint inhibitors (CPI). Methods: Eligible patients (pts) with mUC who progressed on > 1 platinum-based chemotherapy regimen and were CPI naïve were enrolled. Pts were randomized 2:1 to receive eganelisib in combination with nivolumab (EN) or placebo with nivolumab (PN). Pts were stratified by baseline circulating monocytic myeloid derived suppressor cells (mMDSC) level. The primary endpoint was objective response rate (ORR) per RECIST v1.1 in pts with high baseline mMDSC levels. Other endpoints included ORR, progression free survival (PFS) and overall survival (OS) in all pts and PD-L1 +/- pts. Results: We report preliminary data (as of 9/1/2020) for the first 49 pts with 33 randomized to receive EN and 16 PN. Preliminary ORR/PFS is presented in the table below. Except for the mMDSC high subgroup, ORR and PFS were improved in the EN arm compared to the PN arm. The duration of exposure was a median of 15 weeks for EN and 11 for PN. Most common all-Gr AEs (EN vs PN %) were pyrexia (33 vs 0), decreased appetite (30 vs 19), pruritis (24 vs 6), rash (24 vs 6), asthenia (21 vs 31), and transaminase elevation (21 vs 6). Most common Gr≥3 AEs (EN vs PN %) include hepatotoxicity (15 vs 0), transaminase elevation (12 vs 6), and rash (9 vs 0). Following an early safety review, eganelisib dose was reduced from 40 to 30 mg, resulting in a reduction of hepatic AEs. Conclusions: Preliminary data demonstrates that the combination of eganelisib, once reduced to 30 mg, and nivolumab was well tolerated with hepatic and skin-related toxicities more common in the EN arm. When compared to PN, the combination demonstrated an improved ORR and PFS, especially in the PD-L1- subset. Updated efficacy, including PFS and OS, safety and translational data will be presented. Clinical trial information: NCT03980041 . [Table: see text]
177Lu-PSMA-617 (LuPSMA) versus cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) progressing after docetaxel: Updated results including progression-free survival (PFS) and patient-reported outcomes (PROs) (TheraP ANZUP 1603).
Authors: Hofman Michael S , Emmett Louise , Sandhu Shahneen Kaur , Iravani Amir , Joshua Anthony M. , Goh Jeffrey C. , Pattison David A. , Tan Thean Hsiang , Kirkwood Ian D. , Ng Siobhan , Francis Roslyn J. , Gedye Craig , Rutherford Natalie K. , Zhang Alison Yan , McJannett Margaret Mary , Stockler Martin R. , Violet John A. , Williams Scott , Martin Andrew James , Davis Ian D. ,   ANZUP Cancer Trials Group
Published: March 2021

6 Background: TheraP is a randomized phase 2 trial that showed LuPSMA significantly improved the primary endpoint of PSA≥50% reduction (66% vs. 37%) compared to cabazitaxel in men with docetaxel-treated mCRPC. We now report results on other clinical endpoints and PROs reached the pre-specified target of 170 PFS events. Methods: 200 men with mCRPC (median age 72 y, prior enza/abi 91%) and high PSMA-expression by 68Ga-PSMA-11 and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8.5GBq q6wk up to 6 cycles; N = 99) or cabazitaxel (20mg/m2 q3wk up to 10 cycles; N = 101). Secondary endpoints include PSA/radiologic PFS (PCWG3), pain response (≥2 point reduction on McGill-Melzack Present Pain Intensity scale, objective response rate (ORR) (RECIST 1.1), adverse events (CTCAE), PROs (EORTC QLQ-C30) and overall survival (OS). Cut-off date for analysis of 20JUL20. Results: At a median follow-up of 18.4 months, PFS was significantly longer in those assigned Lu-PSMA rather than cabazitaxel (rates at 1y 19% [95%CI 12-27%] vs 3% [1-9%], hazard ratio (HR) 0.63, 95%CI 0.46-0.86; p = 0.003; 173 events). Similar benefit was seen for rPFS (HR 0.64, 95%CI 0.46-0.88; p = 0.007; 160 events) and PSA-PFS (HR 0.60 95%CI 0.44-0.83; p = 0.002; 172 events). ORR in 78 men with measurable disease was significantly greater in the LuPSMA arm (49% vs 24%, RR 2.1, 95%CI 1.1-4.1; p = 0.019). In 90 men with pain at baseline, pain responses occurred in 60% in the Lu-PSMA arm vs 43% for cabazitaxel (RR 1.42, 95%CI 0.84-4.48; p = 0.10). Patient-reported global health status was similar (LuPSMA 64 [95%CI 61-67] vs cabazitaxel 60 [57-64]) with significantly better outcomes reported for fatigue (34 [95%CI 31-37] vs 40 [36-43]), social functioning (79 [76-82] vs 73 [69-77]), insomnia (24 [20-27] vs 29 [25-33]) and diarrhoea (8.3 [5.6-11.0] vs 15.6 [12.6-18.6]) domains. No PRO domains were superior for cabazitaxel. G3-4 AEs were similar to previously reported (33% vs 53%). OS data remains immature (90 deaths). Conclusions: In men with docetaxel-treated mCRPC, LuPSMA is a promising alternative to cabazitaxel with significantly higher activity (PSA≥50%, PFS, ORR), fewer G3-4 AEs, similar effects on global health status, and improvements in some PRO domains. Clinical trial information: NCT03392428.
Biomarker analysis from a randomized phase II study of olaparib with or without cediranib in men with metastatic castration-resistant prostate cancer (mCRPC).
Authors: McKay Rana R. , Radke Marc R , Shyr Yu , Zhao Shilin , Taplin Mary-Ellen , Davis Nancy B. , Monk Paul , Appleman Leonard Joseph , Lara Primo "Lucky" N. , Vaishampayan Ulka N. , Zhang Jingsong , Paul Asit K. , Bubley Glenn , Huang Ying , Shapiro Geoffrey , LoRusso Patricia , Ivy S. Percy , Petrylak Daniel Peter , Swisher Elizabeth M. , Kim Joseph W. 
Published: March 2021

7 Background: We previously reported that cediranib, a vascular endothelial growth factor receptor tyrosine kinase inhibitor, combined with olaparib, a poly (ADP-ribose) polymerase inhibitor, prolonged radiographic progression-free survival (rPFS) compared with olaparib alone in patients with mCRPC. Herein, we present updated clinical data in the overall population and in subgroups by homologous recombination (HR) gene status. Methods: Men with a minimum of one prior line of systemic therapy for mCRPC were randomized 1:1 to receive olaparib 200 mg by mouth twice daily with cediranib 30 mg by mouth daily (C+O) or olaparib 300 mg by mouth twice daily (O). Patients were required to undergo a baseline metastasis biopsy. Next generation sequencing of HR genes was performed on available samples using BROCA-HR assay. HR deficiency (HRD) was defined by presence of homozygous deletions or deleterious mutations in HR genes including BRCA1, BRCA2, ATM, and others. The primary endpoint was rPFS and secondary endpoint was overall survival (OS). Results: Eighty-four patients were included in the analysis of whom 26 patients (31.0%) had HRD mCRPC. The most common HR gene alterations included BRCA2 (n=17, 20%), CDK12 (n=9, 11%), and ATM (n=7, 8%). Consistent with our prior report, in the overall cohort, C+O compared to O resulted in a significant improvement in rPFS (Table). The benefit in rPFS was most pronounced in patients with HRD mCRPC; however, there was no difference between arms in HR proficient (HRP) cancers. Independent of arm allocation, rPFS and OS were numerically longer in patients with HRD mCRPC compared to HRP mCRPC (rPFS: 8.8 versus 4.3 months, p=0.14; OS: 18.6 vs. 12.3 months, p=0.24). Conclusions: C+O improved rPFS in patients with mCPRC compared with O alone. The biomarker analyses revealed that the rPFS benefit of C+O over O is likely driven by patients with HRD mCRPC. Our data warrant validation and support further investigation of the combination of C+O in patients with HRD mCRPC. Clinical trial information: NCT02893917. [Table: see text]