bluuebunny/crossref_metadata_2025_split huggingface dataset:
Outcome of neo-adjuvant chemotherapy in 225 surgical candidates with malignant pleural mesothelioma.
Authors: Kondo Nobuyuki , Nakamichi Toru , Nakamura Akifumi , Kuroda Ayumi , Hashimoto Masaki , Takuwa Teruhisa , Matsumoto Seiji , Okumura Yoshitomo , Kuribayashi Kozo , Kijima Takashi , Tsujimura Tohru , Hasegawa Seiki 
Published: March 2020

8548 Background: Since any surgery for malignant pleural mesothelioma (MPM) are cytoreductive, effective chemotherapy is a prerequisite for surgery. In this context, we give neo-adjuvant chemotherapy (NAC) to all surgical candidates. Methods: Hyogo College of Medicine MPM Surgery Program mandates all surgical candidates to receive NAC, and only patients with stable disease (SD) or better response proceeds to surgery. The program comprised NAC followed by extrapleural pneumonectomy (EPP) and hemithoracic radiation until 2012, and NAC followed by pleurectomy/decortication (P/D) and postoperative chemotherapy thereafter. Eligibility criteria are histologically confirmed non-sarcomatoid MPM, clinically resectable stage (T1-3N0-1M0), performance status 0–1, and no major comorbidity. Results: From December 2006 to December 2018, 225 patients were enrolled. Of 225, 24 patients (10.7%, Group A) did not proceed to surgery because of progressive disease (n=23) or serious adverse events (n=2). Of the remaining 201 patients with partial response (n=38, 16.9%) or stable disease (n=163, 72.4%), 19 refused surgery (Group B), 16 received exploratory thoracotomy (Group C), and 165 completed surgery (Group D, EPP58, P/D107). Surgical mortality rates at 30 and 90 days were 1.1% (n=2) and 2.8% (n=5), and surgical morbidity (≧grade 3) was 26.0% (n=47). Median survival time and survival rates of each group were shown in the table. Briefly, 2-yr survival competed among Group B,C and D, whereas 5-yr survival rapidly dropped in Group B and C. Conclusions: Approximately 90% of MPM patients with surgical intent successfully underwent either of EPP or P/D after effective chemotherapy with acceptable surgical mortality and morbidity. Comparison of patients who refused or accepted surgery suggested that surgery contributed to long-term survival. [Table: see text]
Phase 2 study of tremelimumab plus durvalumab for previously-treated malignant pleural mesothelioma (MPM).
Authors: Venkatraman Deepti , Anderson Adrienne , Digumarthy Subba , Lizotte Patrick H. , Awad Mark M. 
Published: March 2020

8549 Background: Treatment options are limited for patients (pts) with MPM who experience disease progression after first-line pemetrexed-based chemotherapy. This study was designed to explore the activity of combined CTLA-4 + PD-L1 immune checkpoint inhibition using tremelimumab plus durvalumab in previously-treated MPM. Methods: We conducted a phase 2 study of tremelimumab 75 mg plus durvalumab 1500 mg administered intravenously every 4 weeks for four cycles followed by durvalumab maintenance every 4 weeks. Eligible pts had previously received pemetrexed-based platinum doublet chemotherapy and had measurable disease using modified RECIST criteria for mesothelioma. The primary endpoint was overall response rate (ORR) and secondary endpoints were progression-free survival (PFS), overall survival (OS), and duration of response (DoR) as well as safety and tolerability of this combination. A Simon two-stage design was employed to enroll up to 40 patients if 4 or more responses were observed among the first 19 study patients. Pre-treatment, on-treatment, and optional post-progression biopsies underwent flow cytometric immunoprofiling for correlative studies. Results: Among 19 pts enrolled in this study, the best objective response was a confirmed partial response in one patient (5%), stable disease in 9 pts (47%), progressive disease in 8 pts (42%), and not evaluable in one patient. At a median follow-up of 7.1 months, the median PFS was 2.8 months (95% CI 2.04-5.72), and the median OS was 7.8 months (95% CI 6.24-not reached). Of 17 PD-L1 evaluable cases, 10 (59%) were PD-L1 negative, and 7 (41%) had a PD-L1 tumor proportion score of ≥1%. Treatment was generally well-tolerated and there were no treatment-related study discontinuations or deaths. Flow cytometric immunologic changes over the course of treatment associated with disease control will be presented. Conclusions: Tremelimumab + durvalumab was well-tolerated in unselected pts with previously-treated MPM. This study did not meet its primary endpoint. Additional strategies are necessary to develop novel immunotherapeutics and biomarkers of response in MPM. Clinical trial information: NCT03075527.
Impact of large-scale nationwide genomic screening project for small cell lung cancer (LC-SCRUM-Japan).
Authors: Furuya Naoki , Umemura Shigeki , Udagawa Hibiki , Shimokawaji Tadasuke , Seto Takashi , Daga Haruko , Tsuruno Kosuke , Shingyoji Masato , Hara Satoshi , Murakami Haruyasu , Yokouchi Hiroshi , Matsumoto Shingo , Goto Koichi 
Published: March 2020

8559 Background: A variety of genetic analyses have been performed in small cell lung cancer (SCLC), however the clinical relevance of them remains unclear. We prospectively analyzed clinical samples of small-cell lung cancer using a nationwide genomic screening project (LC-SCRUM-Japan). Methods: Submitted tumor samples were subjected to a next-generation sequencing (NGS) system, Oncomine™ Comprehensive Assay, enabling the simultaneous analysis of 143 (ver.1) or 161 (ver.3) cancer-related genes. Results: From July 2015 to January 2019, 707 SCLC patients had been enrolled. The median age was 68 years. 77% were male and 94% were smokers. Among 588 samples completed analysis, we identified high prevalence of inactivating TP53/RB1 mutations in 426 (72%) /194 (33%) of cases, respectively. MYC/MYCL1/MYCN amplifications were detected in 21 (4%) /30 (5%) /9 (2%) of cases, respectively. This NGS analysis also showed that 32 (5%) of cases had well-known genetic alterations in receptor tyrosine kinase genes: 9 EGFR mutations, 9 KRAS mutations and 14 FGFR1 copy number gains. Mutations in the PI3K pathway were detected in 44 (7%) of the tumors. Among them, 8 cases enrolled in the investigator-initiated phase II study of gedatolisib (UMIN 000020585). Survival data was available in 463 patients receiving platinum-based chemotherapy. Multivariate analysis revealed that the presence of PIK3CA mutation (HR; 2.56; 95% CI 1.19 – 5.52; p = 0.016) and MYCN amplification (HR; 4.36; 95% CI 1.91 – 9.97; p < 0.001) were significantly associated with unfavorable survival. The frequency of amplifications in MYC family genes was higher in the samples obtained ≥ 90 days after the first-line platinum-based chemotherapy (18.1%) than in those < 90 days (8.1%, p = 0.01), suggesting MYC family amplification as one of the resistance mechanisms. Conclusions: This large-scale nationwide screening system is helpful for identifying therapeutically relevant genetic alterations, prognostic prediction, and exploring resistance mechanism in SCLC. Updated screening results will be presented at the 2019 ASCO Annual Meeting. Clinical trial information: UMIN000018656.
RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).
Authors: Nakagawa Kazuhiko , Garon Edward B. , Seto Takashi , Nishio Makoto , Ponce Aix Santiago , Chiu Chao-Hua , Park Keunchil , Novello Silvia , Nadal Ernest , Imamura Fumio , Yoh Kiyotaka , Shih Jin-Yuan , Au Kwok Hung , Moro-Sibilot Denis , Enatsu Sotaro , Zimmermann Annamaria H. , Frimodt-Moller Bente , Visseren Grul Carla M. , Reck Martin 
Published: March 2020

9000 Background: Dual blockade of EGFR and VEGFR pathways in EGFRm NSCLC augments anti-tumor efficacy versus (v) EGFR inhibition alone. RELAY (NCT02411448) evaluated efficacy and safety of ERL, an EGFR TKI standard-of-care, plus RAM, a human IgG1 VEGFR2 antagonist, or PL in 1L EGFRm metastatic NSCLC. Methods: Eligibility included untreated metastatic NSCLC pts with Exon 19 deletion (del) or L858R and no CNS metastasis. Randomized (1:1) pts received ERL (150 mg/day) + RAM (10 mg/kg q2w) or ERL + PL, stratified by gender, geographic region (East Asia v other), EGFRm type (Ex19del v L858R) and EGFR testing method (Therascreen/Cobas v other). The primary endpoint was Investigator assessed progression free survival (PFS). Other objectives included ORR, DoR, PFS2, OS, safety, and plasma T790M mutation (Guardant NGS). Results: 449 pts were randomized characteristics were balanced between treatment arms: Asian 77%, Females 63%, Ex19del 54%. RAM + ERL significantly prolonged PFS, DoR, and PFS2 (Table). Grade >=3 TEAEs were greater with RAM (72%) v PL (54%), largely driven by hypertension (24 v 5%, no Gr4); with 1 treatment related on study death (hemothorax) in RAM v 0 PL. EGFR T790M+ rates at progression are forthcoming. Conclusion: RAM + ERL led to superior PFS in 1L EGFRm metastatic NSCLC. Safety was consistent with the established safety profiles of the individual compounds. Clinical trial information: NCT02411448. [Table: see text]
Capmatinib (INC280) in METΔex14-mutated advanced non-small cell lung cancer (NSCLC): Efficacy data from the phase II GEOMETRY mono-1 study.
Authors: Wolf Juergen , Seto Takashi , Han Ji-Youn , Reguart Noemi , Garon Edward B. , Groen Harry J.M. , Tan Daniel Shao-Weng , Hida Toyoaki , De Jonge Maja J. , Orlov Sergey V. , Smit Egbert F. , Souquet Pierre Jean , Vansteenkiste Johan F. , Giovannini Monica , Le Mouhaer Sylvie , Robeva Anna , Waldron-Lynch Maeve , Heist Rebecca Suk 
Published: March 2020

9004 Background: Capmatinib is a highly potent and selective MET inhibitor. Previous data of GEOMETRY mono-1 study showed a clinically meaningful overall response rate (ORR) and manageable toxicity profile in patients (pts) with METΔex14–mutated NSCLC who received 1–2 prior lines of treatment (tx) (Cohort 4) and in particular a high ORR in tx-naïve pts (Cohort 5b). Here we report the results in METΔex14–mutated NSCLC for duration of response (DOR) and progression-free survival (PFS) as well as the updated results for ORR. Methods: GEOMETRY mono-1 is a phase 2, multi-cohort, multicenter study evaluating capmatinib in pts with METΔex14-mutated or MET-amplified advanced NSCLC across 6 cohorts. Pts (≥18 yrs) with ECOG PS 0–1, ALK and EGFR wt, and stage IIIB/IV NSCLC were eligible. Pts with METΔex14 mutation (centrally confirmed) were assigned (regardless of MET amplification status/gene copy number) to Cohorts 4 and 5b and received capmatinib tablets 400 mg BID. Primary endpoint was ORR by Blinded Independent Review Committee (BIRC) per RECIST v1.1. Key secondary endpoint was DOR by BIRC. Results: As of Nov 08, 2018, 97 pts with METΔex14-mutated NSCLC (Cohort 4: 69 pts; Cohort 5b: 28 pts) were evaluable for efficacy. ORR (95% CI) by BIRC was 39.1% (27.6-51.6) in Cohort 4 and 71.4% (51.3-86.8) in Cohort 5b. While still immature at the time of this analysis, data on durability are promising: median DOR (95% CI) by BIRC was 9.72 (4.27-11.14) and 8.41 (5.55-NE) mo for Cohorts 4 and 5b, respectively; median PFS (95% CI) by BIRC was 5.42 (4.17-6.97) and 9.13 (5.52-13.86) mo for Cohorts 4 and 5b, respectively. Safety profile remains favourable and unchanged. Most common AEs (≥25% all grades) across all cohorts (n = 315), were peripheral edema (49.2%), nausea (43.2%), and vomiting (28.3%); majority of the AEs were grade 1/2. Final efficacy analysis (12-mo f-u on DOR) including biomarker data will be presented during meeting. Conclusions: These data confirm capmatinib to be a promising new treatment option for pts with METΔex14-mutated advanced NSCLC regardless of the line of therapy with deep and durable responses and manageable toxicity profile. Clinical trial information: NCT02414139.
Blood tumor mutational burden (bTMB) and tumor PD-L1 as predictive biomarkers of survival in MYSTIC: First-line durvalumab (D) ± tremelimumab (T) versus chemotherapy (CT) in metastatic (m) NSCLC.
Authors: Rizvi Naiyer A. , Cho Byoung Chul , Reinmuth Niels , Lee Ki Hyeong , Luft Alexander , Ahn Myung-Ju , van den Heuvel Michel , Dols Manuel Cobo , Vicente David , Smolin Alexey , Moiseyenko Vladimir , Antonia Scott Joseph , Nakagawa Kazuhiko , Goldberg Sarah B. , Kim Edward S. , Walker Jill , Raja Rajiv , Liu Feng , Scheuring Urban J. , Peters Solange 
Published: March 2020

9016 Background: MYSTIC, an open-label, Ph3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs platinum-based CT, showed an improvement in OS with D vs CT in pts with tumor cell PD-L1 expression ≥25% (PD-L1 TC ≥25%; HR 0.76 [97.54% CI 0.56–1.02], p = 0.036). Exploratory analyses showed bTMB was a predictive biomarker for OS with D±T vs CT. We report further exploratory analyses of OS according to PD-L1 and bTMB. Methods: Immunotherapy/CT-naïve pts with mNSCLC were randomized (1:1:1) to D, D+T or CT. bTMB levels (mut/Mb) were evaluated with the GuardantOMNI platform (Guardant Health), and PD-L1 TC expression with the VENTANA PD-L1 (SP263) IHC assay. Results: D improved OS vs CT in pts with PD-L1 TC ≥25% across bTMB levels (PD-L1 TC ≥25%/bTMB≥20 HR 0.79 [95% CI 0.45, 1.39]; PD-L1 TC ≥25%/bTMB < 20 HR 0.64 [95% CI 0.45, 0.90]). In contrast, D+T improved OS vs CT in pts with bTMB≥20 across different PD-L1 TC expression levels (Table; PD-L1 TC ≥25%/bTMB≥20 HR 0.44 [95% CI 0.23, 0.84]; PD-L1 TC < 1%/bTMB≥20 HR 0.42 [95% CI 0.17, 0.97]). Additional cutoffs and outcomes in subgroups defined by both biomarkers will be presented. Conclusions: These exploratory analyses from MYSTIC support PD-L1 TC expression as an appropriate predictive biomarker for OS with D vs CT, while suggesting bTMB as a predictive biomarker for OS with D+T in mNSCLC. These biomarkers appear to be independent and both may be important for mNSCLC treatment decisions. Interpretation of these data may be limited by small sample sizes; further investigations are warranted. Clinical trial information: NCT02453282. [Table: see text]
Combination of metformin and gefitinib as first-line therapy for nondiabetic advanced non-small cell lung cancer (NSCLC) patients with epidermal growth factor receptor (EGFR) mutations: A multicenter, randomized, double-blind, placebo-controlled phase II trial.
Authors: He Yong , Li Li , Jiang Liyan , Wang Yubo , Zhao Yizhuo , Zhang Xiaoju , Wu Guoming , Zhou Xiangdong , Sun Jianguo , Bai Jun , Ren Biyong , Tian Kun , Xu Zhi , Xiao Hualiang , Zhou Qi , Han Rui , Chen Hengyi , Wang Haidong , Yang Zhenzhou , Gao Chan 
Published: March 2020

9035 Background: Several lines of evidence suggested a role for metformin in sensitizing diabetic NSCLC patients to EGFR tyrosine kinase inhibitors (TKIs). However, data regarding its effects on non-diabetic populations remained scarce. We hereby examined metformin’s first-line use alongside gefitinib in EGFR mutation positive (EGFRm) patients without diabetes. Methods: In this trial (NCT01864681), 224 non-diabetic patients with treatment naïve stage IIIB-IV EGFRm NSCLC were randomly assigned at 1:1 to receive gefitinib plus metformin or placebo. Gefitinib was administered at 250 mg once daily, while metformin/placebo was initiated at 500 mg once daily and then escalated to 1000 mg twice daily over 2 weeks. Dose reduction was permitted for metformin/placebo in case of intolerable toxicity. The primary endpoint was progression-free survival (PFS) rate at 1 year. Secondary endpoints were overall survival (OS), PFS, objective response rate (ORR), and safety. Serum levels of interleukin-6 were also subjected to exploratory analysis. Results: Baseline characteristics were well balanced between treatment groups. The median duration of follow-up was 19.15 (IQR 12.99-28.44) months. The estimated 1-year PFS rate was 41.2% (95% confidence interval [CI] 30.0-52.2) in the metformin group versus 42.9% (95% CI 32.6-52.7) in the placebo group (p = 0.6268). Metformin did not increase median PFS (10.3 months vs. 11.4 months), median OS (22.0 months vs. 27.5 months), or ORR (66.0% vs. 66.7%) over placebo. No significant treatment group differences in terms of PFS were detected across subgroups either, including those with elevated levels of interleukin-6. Metformin plus gefitinib shared a similar safety profile with the control group, except for a remarkably higher incidence of diarrhea (78.38% vs. 43.24%). Conclusions: Our study did not show enhanced gefitinib efficacy upon addition of metformin and hence does not support its concurrent use with first-line EGFR-TKI therapy in non-diabetic EGFRm NSCLC patients. Clinical trial information: NCT01864681.
Evaluating the role of race in outcome of advanced non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitor (ICI): Our institutional experience.
Authors: Nazha Bassel , Chen Zhengjia , Goyal Subir , Engelhart Anne , Carlisle Jennifer Wilkinson , Beardslee Tyler , Gill Harpaul , Odikadze Levani , Liu Yuan , Mishra Manoj K. , Behera Madhusmita , Ramalingam Suresh S. , Owonikoko Taofeek Kunle 
Published: March 2020

9042 Background: Race-based differences in ICI efficacy for advanced NSCLC have not been studied due to under-representation of patients of minority background in pivotal trials. We systematically explored real-world differences in outcome in our diverse patient population. Methods: This is a retrospective review of clinical outcome of patients with advanced NSCLC treated with single-agent ICI between 2013 and July 2018 at the Winship Cancer Institute of Emory University. We performed univariate and multivariate analyses for overall survival (OS) and progression free survival (PFS) patients according to self-reported race and of OS according to gender and PD-L1 expression levels. Results: We analyzed clinical data from 90 eligible patients: Median age of 68.5 yrs, 51% male, White (W)/Black(B)/Asians(A) made up 62.3%/30.7%/5%; 36.5% had brain metastasis at the time of ICI initiation. The majority (85.9%) had ECOG PS ≤2; ICI was 1st line in 15 (16.9%), 2nd line in 59 (66.3%), 3rd line in 12 (13.5%) and nivolumab was the most commonly used agent (41.1%) followed by atezolizumab (32.2%) and pembrolizumab (26.7%). The median OS for the entire population was not reached (NR) (95%CI: 15.6, NR) while 12-month and 24-month OS rates were 63.8% (52.8%, 72.8%) and 53.1% (40.2%, 64.4%). The median OS, 12-month and 24-month OS rates for W and B respectively, were 23.6 months vs. NR; HR: 1.02 (95%CI: 0.51-2.04), p = 0.9571; 61.8% (47.7%, 73.2%) vs. 59.3% (38.6%, 75.0%) and 46.0% (27.9%, 62.4%) vs. 53.9% (32.8%, 70.9%). The overall response rate was 16.7%; 23.8% vs. 11% for B and W respectively. The median duration of response was comparable at 3.36 months vs. 2.94 months for W and B. The median PFS and 12-month PFS rate for W and B respectively were 5.5 (3.2, 14.8) vs. 3.0 (1.4, 10.7) months, p = 0.1350 and 40.0% (27.1%, 52.5%) vs. 29.6% (14.1%, 47.0%). Conclusions: Real-world analysis of our institutional experience showed no significant racial disparity in advanced NSCLC patients treated with ICI. Larger multi-institutional studies to include other US minority population would make our findings generalizable.
Real-world treatment outcome of advanced Chinese NSCLC EGFR exon 20 insertion patients.
Authors: Wang Yan , Yang Guangjian , Li Jun , Xu Haiyan , Yang Lu , Xu Fei , Yang Yaning , Xia Bing , Zhu Viola Weijia , Qiu Weini , Ou Sai-Hong Ignatius 
Published: March 2020

9043 Background: Treatment outcome of advanced EGFR exon20 insertion (ex20ins) patients with 1st- or 2nd-line chemotherapy and EGFR TKIs remains limited. Methods: Retrospective real-world analysis of clinical, molecular, and treatment outcome of a web-based patient registry and hospital chart review. Results: Between 9/13/18-10/22/18, 165 EGFR ex20ins NSCLC patients treated in 99 hospitals from 26 different regions in China were registered. Data cutoff was 12/20/18. EGFR ex20ins were determined by commercial NGS (84%) or PCR (16%). 41 different molecular subtypes of EGFR ex20ins were identified. Ala767_Val769dupASV was the most common (23.0%) followed by Ser768_Asp770dupSVD (17.6%). 61% were females, 77% never-smokers, and CNS mets occurred in 22.4% of patients at time of diagnosis. Median PFS was significantly longer in patients who received 1st-line platinum-based chemotherapy (N = 105) (6.4m; 95% CI:5.7-7.1) vs. EGFR TKI (all generations, N = 23) (2.9m; 95%CI:1.5-4.3; P < 0.001) or vs. EGFR TKI (1G, N = 14) (2.6m; 95%CI:0.8-4.4; P < 0.001). Median PFS was numerically longer in patients who received 2nd-line paclitaxel-based chemotherapy (N = 34) (4.1m; 95%CI:3.3-4.9) versus patients who received 2nd-line EGFR TKIs (N = 18) (2.0m; 95%CI:0.8-3.2; P = 0.342). Patients with CNS mets (N = 21) had shorter median PFS with 1st-line chemotherapy than those without CNS mets (N = 84) (5.5m; 95%CI:0.7-10.3 vs. 6.4m; 95%CI:5.8-7.0; P = 0.694). Patients with CNS mets had numerically shorter median PFS with 1st-line EGFR TKI (N = 7) than those without CNS mets (N = 16) (2.0m; 95%CI:0.8-3.2 vs. 2.9m; 95%CI:2.1-3.7; P = 0.077). Conclusions: Chemotherapy is superior to current approved EGFR TKIs as 1st- or 2nd-line treatment of EGFR ex20ins. Patients with CNS mets had numerically poorer PFS with chemotherapy and EGFR TKI treatment. Targeted therapy against EGFR ex20ins with CNS activity is needed.
Variation in the assessment of immune-related adverse event occurrence, grade, and timing.
Authors: Hsieh David , Watters Mary Katherine , Lu Rong , Xie Yang , Gerber David E. 
Published: March 2020

9047 Background: Accurate assessment of treatment toxicity is critical for patient safety, balancing clinical utility, and understanding treatment impact. Given their unpredictability and heterogeneity, immune-related adverse events (irAEs) may be particularly challenging to ascertain. Our objective was to evaluate the agreement between clinicians on the occurrence, grade, and timing of irAEs, and elucidate determinants of discordance. Methods: We performed a retrospective cohort study of 52 patients with cancer treated with immune checkpoint inhibitors at a National Cancer Institute-designated comprehensive cancer center. Two medical oncologist observers used algorithm-driven manual chart review to characterize eight well-described irAEs (adrenal insufficiency, colitis, hepatitis, hyperthyroidism, hypophysitis, hypothyroidism, pneumonitis, rash). Inter-rater agreement for incidence, severity, and timing of irAEs was determined using Cohen's kappa coefficient (κ) and weighted κ with linear weights. Results: The incidence of irAEs ranged from 4-35% for observer 1 and 6-27% for observer 2, while aggregate incidence rates ranged from 8% (hypophysitis) to 40% (pneumonitis). Inter-rater agreement was generally limited for irAE incidence (κ 0.37 [hypophysitis]-0.8 [hypothyroidism]). Weighted κ similarly showed limited or poor agreement for most irAE grades (κ 0.31-0.75). Differences in the assessment of irAE time of onset ranged from 5-188 days. Rates of discordance were greater for grade 1 (39%) and grade 2 (41%) irAEs than for grade 3-4 (20%) irAEs. Multivariable analyses showed that longer therapy duration (OR 4.8, P= 0.02) and a high Charlson Comorbidity Index (OR 4.09, P= 0.03) were significantly associated with discordant irAE assessment. Conclusions: Inter-rater reliability varied among irAEs and consistently showed poor agreement for the incidence, severity, and timing of irAEs. Agreement was greater for irAEs with distinct laboratory-based definitions (eg, hypothyroidism), higher-grade irAEs, and irAEs in patients with fewer comorbidities and shorter immunotherapy duration. These findings have implications in the clinical management of patients receiving immunotherapy and in the reporting of immunotherapy clinical trials.