tbuckley/cabot-search huggingface dataset:
Phase 2 study of pembrolizumab plus pemetrexed for older patients with non-squamous non-small cell lung cancer with PD-L1 tumor proportion score of less than 50%: CJLSG1901.
Authors: Yoshihito Kogure, Hiroya Hashimoto, Haruko Daga, Yasushi Fukuda, Akihiro Bessho, Tadaaki Yamada, Yukihiro Toi, Tomoki Kimura, Hiroshige Yoshioka, Koichi Azuma, Naoki Furuya, Yasutaka Fukui, Hideo Saka, Masashi Kondo
Journal: Journal of Clinical Oncology (2024)

8540 Background: Immune checkpoint inhibitor plus platinum-containing chemotherapy is the standard of care for patients with advanced non-small cell lung cancer (NSCLC). Pembrolizumab combined with pemetrexed and cisplatin/carboplatin is approved as first line treatment for patients with metastatic non-squamous NSCLC based on the results of KEYNOTE-189. However, data on the efficacy and safety of this regimen are limited for patients aged ≥75 years. In preclinical models, anti-PD-L1 antibody with pemetrexed enhanced the antitumor effect more than the combination of pemetrexed with carboplatin. These results suggest that pembrolizumab plus pemetrexed can be effective while potentially sparing severe side effects by omitting carboplatin. Methods: This multicenter, open-label, phase 2 trial was conducted at 42 institutions in Japan to evaluate the efficacy and safety of pemetrexed plus pembrolizumab. Eligible patients had metastatic/recurrent non-squamous NSCLC without sensitizing EGFR or ALK mutations, were aged ≥75 years, had a PD-L1 TPS of less than 50%, had received no prior systemic chemotherapy, and had an ECOG performance status of 0 or 1. Patients received pemetrexed (500 mg/m 2 ) plus pembrolizumab (200 mg/body) on day 1 of each 21-day cycle. Treatment continued until radiographic progression or unacceptable toxicity was observed. The primary endpoint was the objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. This trial is registered with ClinicalTrials.gov (NCT04396457) and the Japan Registry of Clinical Trials (jRCTs041200012). Results: From July 2020 to May 2022, 49 patients were enrolled in this study. The median follow-up time was 15.4 months. The median age was 79.0 years (range 75-91), 77.6% of the patients were male, and 57.1% had a PD-L1 TPS ≥1%. The ORR was 36.7% (95% CI 23.4-51.7), and the disease control rate was 65.3% (95% CI 50.4-78.3%). The median PFS was 7.6 months (95% CI 4.8-16.2), and the median OS was 19.4 months (95% CI 11.8- not reached). The most common grade 3 or 4 adverse events were neutropenia (31.3%), leukopenia (20.8%), and anemia (12.5%). Serious adverse events were observed in 14 patients (4 with pneumonitis, 2 with decreased appetite, 2 with febrile neutropenia). No treatment-related deaths were observed. Conclusions: Pembrolizumab plus pemetrexed demonstrated an ORR of 36.7% and met the primary endpoint. The safety profile was tolerable and manageable. This combination therapy is a promising candidate as a novel first line treatment strategy for older patients with metastatic non-squamous NSCLC. Clinical trial information: NCT04396457 .
Differentiating between adrenocortical carcinoma and pheochromocytoma by radiomics features at CT: A multi-institutional retrospective study.
Authors: Jingtong Zhang, Yinyao Chao, Kai Yao, Shengjie Guo
Journal: Journal of Clinical Oncology (2024)

4603 Background: Adrenocortical carcinoma (ACC), a highly malignant and rare tumor of the adrenal gland, shares similar CT characteristics with the less malignant pheochromocytoma (PHEO), resulting in low CT diagnostic accuracy. The standard therapeutic strategy for ACC differs from that of PHEO, making accurate diagnosis of ACC challenging but important. Radiomics offers an opportunity to classify adrenal tumors. However, previous research has primarily focused on differentiating malignant adrenal lesions from benign cases. In addition, the rarity of ACC makes it difficult to initiate large-scale studies, thus hindering further applications of radiomics. This study aimed to differentiate between ACC and PHEO using radiomics features based on contrast-enhanced CT. Methods: A total of 158 patients (median age, 47 years; inter-quartile range, 32-57 years; 76 males) pathologically diagnosed with ACC or PHEO between 2011 and 2023 were enrolled from three independent institutions. Radiomics features were extracted from different phases of contrast-enhanced CT images, and then selected by a two-step procedure. The radiomics model was developded and trained in the development cohort of 109 patients from Institution 1, then the model performance was tested in the test cohort of 49 patients from Institution 2 and 3. The area under the receiver operating characteristic curve (AUC) of the radiomics model was compared with two radiologists using the DeLong test. The SHAP method was used to improve the interpretability of the radiomics model. Results: We developed and tested a radiomics model that consisting of 10 selected radiomics features. In the test cohort, the radiomics model exhibited a significant improvement in diagnostic performance over 2 radiologists (AUC 0.92 vs. 0.79, 0.63) and achieved high accuracy (86%), sensitivity (81%) and specificity (88%) in differentiating between ACC and PHEO. Furthermore, the diagnostic process of this radiomics model was visualized using the SHAP method. Conclusions: To our knowledge, this is the first multi-institutional study to develop an interpretable radiomics model for preoperative differentiation between ACC and PHEO based on contrast-enhanced CT. The diagnostic performance of the radiomics model surpassed that of experienced radiologists, which may aid clinical decision making and improve treatment outcomes for ACC.
Precision medicine in NSCLC: Challenges and practice gaps in community cancer clinics.
Authors: Nikoletta Sidiropoulos, Julie R. Brahmer, Janet Storey, Ilona Dewald, Samuel Dooyema, Jeffrey D. Carter, Cherilyn Heggen, Kelly E. McKinnon
Journal: Journal of Clinical Oncology (2024)

8589 Background: Current guidelines for clinical management of advanced NSCLC recommend testing for nine molecular alterations in addition to PD-L1, to identify appropriate patients for targeted therapies. This quality improvement initiative evaluated current practice patterns in biomarker testing in NSCLC in community oncology clinics. Methods: In 2023, 68 healthcare providers (HCPs) from 6 clinics completed surveys on biomarker testing, treatment decision making, and patient-centered care in NSCLC. Teams from each clinic (N=98) then participated in audit/feedback (AF) sessions to assess site-specific gaps and develop and implement action plans for improvement. Results: Many advanced NSCLC patients did not receive the recommended biomarker tests (Table). This is likely related to low rates of next-generation sequencing (NGS) based testing: only 45% or 30% of patients received DNA-based or RNA-based NGS, respectively. Most HCPs (72%) reported testing at time of diagnosis, and about one-third also tested at time of disease progression. However, 48% of HCPs were very/extremely likely to start treatment before receiving molecular test results, and 49% said that "determining whether to begin treatment prior to receipt of molecular testing results" was their top challenge in NSCLC care. Rates of targeted therapy receipt were low, with 33% of HCPs reporting that fewer than half of their patients with an actionable mutation received the corresponding agent. Providers believed "improved collaboration across interprofessional teams" (24%) and "integration of multidisciplinary tumor boards into treatment planning" (22%) would most improve care for NSCLC patients. To address identified gaps, teams developed action plans, including establishing new workflows to better incorporate molecular testing and designating a team member to facilitate multidisciplinary collaboration. Following the AF session, providers reported high confidence in selecting appropriate biomarker tests (83%) and biomarker-directed therapies (75%) for patients with NSCLC . Full findings will be presented, along with follow-up surveys measuring real-world impact of the system-level practice changes. Conclusions: Although most HCPs used some form of molecular testing in NSCLC, testing was not as comprehensive as current guidelines recommend. Through this QI initiative, teams identified gaps/barriers in their own practices, and developed and implemented action plans for improvement. These data and actionable insights support effective and evidence-based integration of biomarker testing in advanced NSCLC to optimize patient outcomes that can help inform improvement strategies for NSCLC care teams in community settings nationwide. [Table: see text]
Sotorasib plus panitumumab for pre-treated non-small cell lung cancer with <i>KRAS</i>G12C mutation: A phase 1b study.
Authors: Corey J. Langer, Rachel Galot, Hans Prenen, David S. Hong, Iván Victoria, Ravi Salgia, Maxime Chenard-Poirier, Muhammad Furqan, Emily Chan, Jane Nolte-Hippenmeyer, Caihong Xia, Bob T. Li
Journal: Journal of Clinical Oncology (2024)

8559 Background: Sotorasib, a selective and irreversible KRAS G12C inhibitor, is approved for treatment of adults with KRAS G12C-mutated advanced non-small cell lung cancer (NSCLC) who received ≥ 1 prior systemic therapy. EGFR pathway alterations have been observed as an acquired resistance mechanism with sotorasib monotherapy. Treatment with sotorasib plus an EGFR inhibitor, such as panitumumab, may enhance efficacy over sotorasib monotherapy, as demonstrated in chemotherapy refractory metastatic colorectal cancer. Our current study assesses sotorasib plus panitumumab in pre-treated advanced NSCLC. Methods: Key eligibility criteria for this dose expansion cohort of the CodeBreaK 101 study (NCT04185883) included advanced NSCLC positive for KRAS G12C, ≥ 1 prior treatment for advanced disease, and no prior KRAS G12C inhibitor exposure. Patients (pts) with active brain metastases were excluded. Primary endpoint was safety. Secondary endpoints included investigator-assessed objective response rate (ORR), disease control rate (DCR), duration of response (DOR), time to response (TTR), progression free survival (PFS), as well as overall survival (OS). Results: As of January 11, 2024, 40 pts (median age, 67.5 years; 55% female) received oral sotorasib 960 mg daily and panitumumab IV 6 mg/kg every 2 weeks. 43% of pts had a history of brain metastases. Median number of prior lines of therapy was 1; 42% received ≥ 2 regimens and 38% had disease progression as their best response to last line of therapy. Most pts received anti-PD-(L)1 therapy (90%), platinum-based chemotherapy (85%), or both (78%). Most common (&gt; 30%) treatment-related adverse events (TRAEs) attributed to any study drug were: diarrhea in 19 (48%) pts, dermatitis acneiform in 18 (45%), and dry skin in 16 (40%). Most common grade ≥ 3 TRAEs were increased ALT and AST in 7 (18%) and 4 (10%) pts, respectively, dermatitis acneiform in 5 (13%), diarrhea in 3 (8%), and hypomagnesaemia in 2 (5%) pts. Overall response rate was 45% (all partial responses), with a DCR of 90% (Table). Median PFS was 5.8 months (median follow-up 14.0 months). At a median follow-up of 11.0 months, OS data were not yet mature. Conclusions: This cohort of sotorasib plus panitumumab in pre-treated patients with KRAS G12C advanced NSCLC demonstrated safety consistent with each drug's profile. The ORR appears promising in this pretreated population and may warrant further investigation. Clinical trial information: NCT04185883 . [Table: see text]
<i>FGFR3</i>-mutated urothelial carcinoma of bladder and upper tract including ureter and renal pelvis: A comparative genomic profiling study.
Authors: Michael Basin, Rebecca A Sager, Dean Pavlick, Andrea Necchi, Philippe E. Spiess, Roger Li, Ashish M. Kamat, Petros Grivas, Liang Cheng, Douglas I. Lin, Jeffrey S. Ross, Gennady Bratslavsky, Joseph M Jacob, Shilpa Gupta, Neeraj Agarwal, Alina Basnet
Journal: Journal of Clinical Oncology (2024)

4588 Background: Activating DNA sequence genomic alterations (GA) in the FGFR3 gene are known oncodrivers and relevant precision targets for patients with urothelial carcinoma. THOR-1 trial showed a significant overall survival benefit with erdafitinib (FGFR inhibitor) vs chemotherapy (taxane or vinflunine) in patients with advanced urothelial carcinoma of the bladder (UCB) or upper tract urothelial carcinoma (UTUC). PROOF-302 trial showed higher frequency of FGFR3 GA in UTUC (30%) vs UCB (13%). We sought to explore differences in frequency of FGFR3 alterations and the genomic landscapes of FGFR3-altered UCB, ureteral urothelial carcinoma (UUC) and renal pelvic urothelial carcinoma (RPUC). Methods: 10,798 UCB and 2,392 UTUC (871 UUC and 1521 RPUC) underwent hybrid capture-based comprehensive genomic profiling (CGP) to assess all classes of GA and measure MSI status, TMB level, genomic ancestry, genomic signature, germline mutations and HRD score. PD-L1 was determined by IHC Dako 22C3 using the TPS system. Results were compared using the Fisher Exact method with the Benjamini-Hochberg adjustment. Results: FGFR3mut+ status was significantly higher in RPUC (27.8%), followed by UUC (22.0%), and UCB (18.1%) (P&lt;.0001) (Table). Patients with UCB were more often male compared to patients with UTUC. Median age, EUR ancestry, and GA/tumor were similar. “Targetable” GA in ERBB2 (P=.03), PIK3CA(P=.05), KDM6A (P=.0009) were more frequent in FGFR3mut+ UCB vs FGFR3mut+ UTUC. Targetable GA in PTEN, TSC1 and MTAP currently associated with drugs tested in trials were similar in UBC and UTUC. The KEGG ERBB and VEGF signaling pathways were more frequently identified in UCB (P=.036) and the MMR pathway more frequently identified in UTUC (P=.014). The HRD signature was similar in the groups. MSI-high status was significantly higher in UTUC vs UCB, but there was no significant difference in TMB or PD-L1 expression levels. Conclusions: Although histologically similar, the genomic landscape of FGFR3mut+ RPUC and UUC has notable differences with FGFR3mut+ UCB. Limitations include lack of clinical data annotation, inherent selection biases, and the retrospective nature of this work. Findings may impact clinical trial designs for UCB and UTUC, including evaluating combinations of anti-FGFR3 with other agents. CGP may also inform resistance mechanisms and putative biomarkers of response. [Table: see text]
Survival differences in advanced non-small cell lung cancer after developments in regimens with immune check point inhibitors: Population based retrospective study from United States SEER database.
Authors: Binay Kshetree, Supradepti Bhandari
Journal: Journal of Clinical Oncology (2024)

e20516 Background: Metastatic non-small cell lung cancers (NSCLC) are being treated with immune checkpoint inhibitors (ICI). Nivolumab was approved in 2015, pembrolizumab (pz) /atezolizumab (az) in 2016, pz-chemotherapy (Ch) (pemetrexed + carboplatin) in 2017; durvalumab, pz-Ch (paclitaxel) and az-Ch (bevacizumab, carboplatin, paclitaxel) in 2018. We aim to study population based overall survival (OS) differences before and after these approval. Methods: We used Surveillance, Epidemiology and End Results (SEER) research plus database (Nov 2022 submission,17 registries). Patients aged ≥ 20 years with NSCLC as “distant” (combined summary stage) from 2013-2018 were included. Time was stratified as Pre-ICI from 2013-2014, initial single agent ICI from 2015-2016 (ICI) and new ICI/ICI-Ch from 2017-2018 (n/ICICh). OS in these time periods was calculated using Kaplan Meier (KM) method and were compared with log rank tests. Multivariate analysis was done using cox proportional hazard ratios. p &lt; 0.05 was considered for statistical significance. IBM SPSS was used for analysis. Results: Total of 6375 patients had advanced NSCLC from 2013-2018. 4 and 5-year survival from 2017-2018 was not available due to data up to 2020. The survival difference among three timelines was statistically significant (log rank test, χ 2 = 20.795, p &lt; 0.001). On multivariate analysis, ICI and n/ICICh had significantly lower risk of dying as in table compared to Pre-ICI. Male, age ≥50 years, Black/Asian/Pacific Islanders were at higher risk and who received radiotherapy/chemotherapy had a lower risk of dying. There was no significant difference among Hispanic versus non-Hispanic and among marital status. Conclusions: ICI shows clear survival benefits in advanced NSCLC in this population-based study which supports clinical trials. Racial, gender and older age disparities shown in this study will further help in guiding appropriate measures. Future analysis with new ICI/Ch therapy with new timelines will help show population-based survival benefits after updated database. [Table: see text]
Pre- and post-operative lung cancer recurrence prediction following curative surgery: A retrospective study using European radiomics and clinical data.
Authors: Ann Valter, Tanel Kordemets, Aydan Gasimova, Noah Waterfield Price, Lutz Freitag, Anil Vachani, David Paul Carbone, Kersti Oselin
Journal: Journal of Clinical Oncology (2024)

8066 Background: Accurately estimating the risk of lung cancer recurrence is vital for making informed treatment choices, both before surgery, such as the prescription of neo-adjuvant/peri-operative therapies and the extent of lung resection, and after surgery, such as the prescription of adjuvant therapies and planning follow-up strategies. In this study, we build on previous work demonstrating the predictive power of pre-operative patient demographic and imaging features and develop a machine-learning model using a combination of clinical and tumour radiomic features in the pre- and post-operative setting. Methods: We collected a dataset of 323 clinical stage I-IIIA lung cancer patients who underwent surgical treatment for lung cancer, of which 94 had lung cancer recurrence. This includes retrospectively collected CT images and associated patient demographic and diagnostic data from North Estonia Medical Centre (NEMC). The models were trained to predict the likelihood of recurrence on a diverse set of features, including radiomic features extracted from CT images and relevant clinical variables. Post-operative clinical factors such as pathological staging and tumor histology were only included in the post-operative model. An 8-fold cross-validation strategy was used, where, in each fold, 6 (of the 8 equally sized) subsets were used for training, one for model tuning, and one for validation. As a baseline, we compare the pre- and post-operative models to clinical and pathological staging, respectively. Performance was evaluated using the Area-Under-the-ROC-Curve (AUC) and sensitivity (at a fixed specificity of 90%). Results: Lung cancer recurrence classification results are tabulated below for the pre-operative models. We find that the pre-operative model (AUC=74.1%, Sens=35.29%) performs significantly better than clinical staging alone (AUC=65.4%, Sens=14.71%, p=0.025), and that the post-operative model (AUC=74.4%, Sens=26.47%) performs significantly better than pathological staging alone (AUC=67.3, Sens=22.4%, p=0.045). Top predictive features for both the pre-operative and post-operative models included clinical staging, tumor shape and textural radiomics, tumor size and tumor location. The post-operative model additionally included pathological staging and tumor histology. Conclusions: Based on this retrospective analysis, we find that the model outperforms staging prediction of lung cancer recurrence in pre- and post-operative settings. With further development, these algorithms could prove a valuable tool to aid the management of lung cancer patients. [Table: see text]
Disparities in trends in bladder cancer mortality between urban and rural patients: A 2000-2020 analysis.
Authors: Abdul Rahman Al Armashi, Marisa Thierheimer, Laura Bukavina, Adam C. Calaway, Randy Vince, Prateek Mendiratta, Jorge A. Garcia, Jason R Brown
Journal: Journal of Clinical Oncology (2024)

4583 Background: Patients in rural areas in the US often have worse healthcare outcomes due to socioeconomic deprivation, higher rates of smoking, and limited access to medical care. Despite a general decline in bladder cancer mortality over the past two decades, comprehensive studies comparing these trends between urban and rural mortality are scarce. Methods: Utilizing the CDC WONDER database, we extracted mortality data for bladder cancer from 2000 to 2020. Age-adjusted mortality rates per 100,000 persons were standardized to the Year 2000 US standard population. Data segmentation by urbanity utilized the 2013 National Center for Health Statistics Urban-Rural Classification Scheme. The National Cancer Institute's Joinpoint Regression Program was employed to calculate average annual percent changes (AAPCs) and annual percent changes (APCs). Results: In our analysis, we identified a total of 306,750 bladder cancer death cases from 2000 to 2020. Significant improvements in bladder cancer mortality were observed in urban areas, with large central metros experiencing the most pronounced decrease (AAPC -1.0%, p&lt;0.001). This decline was moderate between 2000 and 2016 (APC -0.3, p&lt; 0.001) but accelerated between 2016 and 2020 (APC -3.8%, p&lt;0.001). Large fringe and medium metros also saw comparatively smaller but significant declines (AAPC -0.6%, P&lt;0.05) and also accelerated between 2016-2020. In contrast, small metro and rural areas (micropolitan and noncore) showed no significant improvement, with mortality rates remaining stable between 2000 and 2020 (AAPC 0.2%, P=0.099). Conclusions: This analysis, the largest to date comparing urban and rural mortality trends in bladder cancer, highlights significant disparities in outcomes between large urban and rural areas. The marked improvement in urban areas, especially noted around the time novel agents such as immunotherapy were introduced, underscores the potential impact of advanced treatments. However, the stable mortality rates in rural areas suggest that access to advanced care, environmental influences, socioeconomic status, and slower adaptation of new guidelines in rural settings may play critical roles. These findings underline the urgent need for strategies to close the urban-rural gap. [Table: see text]