tbuckley/cabot-search huggingface dataset:
Phase 1/2 trial of the XPO1 inhibitor selinexor in combination with docetaxel in previously treated, advanced <i>KRAS</i> mutant non-small cell lung cancer (NSCLC).
Authors: Mitchell S. von Itzstein, Timothy F. Burns, Jonathan Dowell, Leora Horn, David Ross Camidge, Sally J. York, Keith D. Eaton, Christopher James Walker, Song Zhang, David E Gerber
Journal: Journal of Clinical Oncology (2024)

8597 Background: KRAS mutant NSCLC remains a therapeutic challenge. Although KRAS G12C inhibitors are now approved for cases harboring that specific mutation, their efficacy is modest and the G12C variant accounts for only 40% of KRAS mutations in NSCLC. To date, there are no approved targeted therapies for non-G12C KRAS mutant NSCLC. Selective inhibitors of nuclear export (SINE) modulate cancer cell biology by retaining certain proteins—such as tumor suppressors—within the nucleus, where they remain physiologically active. The XPO1 inhibitor selinexor demonstrated efficacyinpreclinicalNSCLC models harboring various KRAS mutations. Methods: In this 3 + 3 dose-escalation phase 1/2 trial, patients with previously treated advanced KRAS mutant NSCLC received selinexor (dosed orally weekly) plus docetaxel 75 mg/m 2 IV every three weeks (NCT03095612). Prior treatment with KRAS G12C inhibitors was permitted. Results: Among 40 enrolled patients, median age was 66 years, 22 (55%) were female, and 34 (85%) were white. KRAS mutation types included G12C (28%), G12V (23%), G12D (20%), G12A (13%), G12R (5%), G13C (5%), and one case each of G12S, G13D, Q61L, and K117N. Patients had received a median of 2 prior lines of therapy (range 1-4). The maximum tolerated dose of selinexor was 60 mg PO weekly combined with docetaxel. The most common adverse events (AE) were nausea (73%, Gr ≥3 8%), fatigue (70%, Gr ≥3 5%), neutropenia (65%, Gr ≥3 60%), diarrhea (58%, Gr ≥3 10%), anorexia (50%, Gr ≥3 0%), and vomiting (45%, Gr ≥3 5%). Of 32 patients evaluable for efficacy, 7 (22%) had partial response (PR) and 18 (56%) had stable disease (SD) as best response. Median progression-free survival (PFS) was 4.1 months (95% CI, 2.9-5 months); median overall survival (OS) was 7.1 months (95% CI, 4.5-13.7 months). Clinical outcomes did not differ significantly among KRAS mutation types. However, TP53co-mutations (48%) were associated with significantly worse outcomes: disease control rate (PR + SD) 27% vs 92% ( P=0.006); median PFS 1.8 vs 7.4 months ( P&lt;0.001); median OS 5.8 vs 17 months ( P=0.006). Additional biomarker studies are ongoing. Conclusions: Selinexor plus docetaxel is tolerated with multi-agent supportive care. The combination shows moderate efficacy across KRAS mutation types, with promising activity in TP53 wild type cases. Clinical trial information: NCT03095612 .
Cracking the code: Can bibliometric attributes predict NIH R01 grant funding outcomes in gastrointestinal oncology? Exploring patterns from a five-year analysis.
Authors: Sara Ahmed Khan, Faraz Eshaghi, Mohammed Z Rehman, Serena Kotwal, Amy Salama, Kainat Khan, Muhammad Zain Farooq, Kapisthalam Kumar
Journal: Journal of Clinical Oncology (2024)

9051 Background: The allocation of National Institutes of Health (NIH) R01 grants holds paramount importance for principal investigators in the field of scientific research. In this study, we explore the relationship between bibliometric attributes of principal investigators- specifically H-index, citations, publications, and seniority with the amount of NIH grant funding for R01 grants under gastrointestinal oncology from the fiscal years of 2018 to 2022. Understanding these interrelationships is crucial for researchers aiming to enhance their profiles to secure higher funding amounts from the NIH. Methods: The data was retrieved from the NIH RePORTER (Research Portfolio Online Reporting Tools Expenditure) using gastrointestinal oncology-related search terms from 2018-2022. The number of citations, publications, H-index, and seniority were obtained from Scopus. The bibliometric attributes of principal investigators were correlated with NIH grant funding amounts. Multiple regression analysis was employed to quantify the predictive power. Additionally, t-tests were performed to examine the significant differences in grant funding between high and low h-index groups. Results: A total of 1652 principal investigators who were awarded a gastrointestinal oncology related R01 grant were included in this study. The H-index consistently showcases a positive correlation with the amount of grant funding, reaching statistical significance in 2020 (H-index coefficient=1510.49, p value=0.07). Concurrently, t-tests emphasize the importance of H-index, illustrating that PI’s with high H-indexes (H-index &gt;42) secure significantly higher funding (average grant=$423,806, p=0.006 compared to those in the lower H-index group (average grant=$420,306, p=0.004). Conversely, citations showcased mixed results, with 2020 revealing a significant negative correlation (coefficient: -1.63, p= 0.04). Publications displayed a strong positive effect in 2021 (coefficient: 231.68, p value=0.10). Seniority exhibited varying impacts across years, notably a significant negative relationship in 2018 (coefficient: -3013.9, p=0.025). Conclusions: This study illuminates the complex interplay between PI’s bibliometric attributes and NIH grant funding outcomes. Notably, high h-index values consistently correlate with a higher funding amount for NIH grants. Although these insights contribute to a deeper understanding of the factors influencing NIH grants, further analysis should investigate additional variables that may significantly impact NIH grant funding.
PD-L1 and alternative immune checkpoints (AICs) in non-small cell lung cancer (NSCLC): Insights into the tumor immune microenvironment (TIME) and immunotherapy (IO) outcomes.
Authors: Angelica D'Aiello, Shayan Nazari, Hyein Jeon, Andrew Elliott, Ari M. Vanderwalde, Hossein Borghaei, Stephen V. Liu, Xingxing Zang, Balazs Halmos, Haiying Cheng
Journal: Journal of Clinical Oncology (2024)

8531 Background: PD-L1 and recently identified AICs (B7x, B7-H3, and HHLA2) may function as key immune evasion mechanisms in NSCLC and influence IO efficacy. This study explores the expression patterns of PD-L1 and AICs within the TIME and their impact on IO outcomes in NSCLC, including key molecular subtypes. Methods: NSCLC samples (n=27,629) were analyzed (Caris Life Sciences) with NextGen Sequencing on DNA (592 genes or whole exome)/RNA (whole transcriptome). Tumor cell PD-L1 expression (22c3) was assessed by IHC. Gene expression profiles were analyzed for IFN-γ score and QuantiSEQ was used to assess immune cell infiltration in the TIME. Real-world overall survival (rwOS: from time of biopsy to last contact), time on treatment [TOT: from the first pembrolizumab (pembro) treatment to the last], and OS on pembro (OSpem: from pembro start to last contact) were calculated. Mann-Whitney U, X2/Fisher-Exact, and log-rank tests were applied where appropriate. Results: PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA expression had higher IFN-γ score and immune cell fractions (p&lt;0.0001 for both) vs PD-L1 IHC- and low expression, respectively. Additionally, PD-L1 IHC+ NSCLC was associated with (a/w) higher median transcript levels (TPM) of PD-L1 and B7-H3, while PD-L1 IHC- NSCLC was a/w higher TPM of HHLA2 and B7x (p&lt;0.0001 for all). AICs expression varied by molecular subtype, e.g., higher HHLA2/B7x RNA in EGFR mutant vs wild-type (WT) NSCLC. Moreover, PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA and low B7H3 RNA were a/w longer rwOS, OSpem, and TOT; high HHLA2 RNA was a/w longer rwOS and OSpem with similar TOT; and low B7x RNA expression was a/w longer OSpem and TOT with similar rwOS (Table). Conclusions: Both PD-L1 IHC+ NSCLC and cases with high PD-L1 RNA expression are a/w a more inflammatory TIME, and superior survival and IO outcomes. Moreover, consistent with our prior HHLA2 IHC work (PMIDs: 27553831, 29374053), HHLA2 RNA expression was significantly higher in PD-L1 IHC- and EGFR mutant cases. These findings support the potential utility of transcriptomics along with protein expression for assessing novel predictive biomarkers for IO. Furthermore, the distinct expression profiles of AICs identified in our study may represent key subtypes mediating IO response in WT and EGFR mutant NSCLC. [Table: see text]
Sacituzumab govitecan (SG) + pembrolizumab (pembro) in first-line (1L) metastatic non-small cell lung cancer (mNSCLC) with PD-L1 ≥ 50%: Cohort A of EVOKE-02.
Authors: Jyoti D. Patel, Byoung Chul Cho, Manuel Cobo, Roxana Reyes Cabanillas, David Vicente, Jose Fuentes Pradera, Edward B. Garon, Tony S. K. Mok, Federico Cappuzzo, Joel W. Neal, Sabeen Fatima Mekan, Farnoush Safavi, Nelumka Fernando, Michael Jon Chisamore, Martin Reck
Journal: Journal of Clinical Oncology (2024)

8592 Background: SG, a Trop-2–directed antibody-drug conjugate, has clinical activity and manageable safety in heavily pretreated patients with mNSCLC. EVOKE-02 (NCT05186974) is an ongoing, global, open-label, multicohort phase 2 study evaluating SG + pembro ± platinum agent as 1L treatment for mNSCLC. We report safety and efficacy results from Cohort A of EVOKE-02, with a median follow-up of 11.3 months. Methods: Patients aged ≥18 years with no prior systemic mNSCLC treatment, no actionable genomic alterations, and an ECOG performance status of 0 or 1 were enrolled into Cohort A [PD-(L)1 tumor proportion score ≥50%, 22C3 assay]. Patients received SG 10 mg/kg intravenously on days 1 and 8 + pembro 200 mg intravenously on day 1 of 21-day cycles. Primary endpoints include objective response rate (ORR; RECIST v1.1) per independent review committee (IRC); secondary endpoints include progression-free survival (PFS), duration of response (DOR), disease control rate (all per IRC), overall survival (OS), and safety. Results: As of December 1, 2023, 30 patients in Cohort A were enrolled and had received SG + pembro. Median age was 67 (range, 47-77) years; 60% had nonsquamous histology and 80% had an ECOG performance status of 1. Among all treated patients (n=30), ORR was 67% (95% CI, 47-83%) (squamous, 67% [95% CI, 35-90%]; nonsquamous, 67% [95% CI, 41-87%]). Median PFS was 13.1 (95% CI, 5.5-not reached [NR]) months (squamous, NR [95% CI, 1.2-NR] months; nonsquamous, 13.1 [95% CI, 5.5-NR] months). Median DOR was NR. In the safety population (n=30), the incidence of grade ≥3 treatment-emergent adverse events (TEAEs) and of grade ≥3 TEAEs related to any study drug were 67% and 40%, respectively. Grade ≥3 TEAEs in ≥10% of patients were neutropenia (17%), diarrhea (10%), and respiratory failure (10%). TEAEs leading to SG discontinuation occurred in 17%. There was 1 (3%) treatment-related death due to neutropenic sepsis. Conclusions: SG + pembro demonstrated promising activity in patients with tumor proportion score ≥50% mNSCLC. AEs were manageable and consistent with the known safety profile of each individual agent. The EVOKE-03 study (NCT05609968) of pembro vs SG + pembro in mNSCLC is ongoing. Clinical trial information: NCT05186974 . [Table: see text]
Formation and evaluation of the ASCO medical education community of practice (Med Ed CoP).
Authors: Sam Brondfield, Rami Manochakian, Katherine Jean Walsh, Maria Quintos Baggstrom, Elizabeth Henry, Aparna Raj Parikh, Deepa Rangachari, Maura Meredith Barry, Jennifer Gao, Meredith Elana Giuliani, Annie P. Im, Kristen A. Marrone, Mairead Geraldine McNamara, Martina Cathryn Murphy, Lori J Rosenstein, Brian Russell, Jennifer Tseng, Jennifer E. Schwartz
Journal: Journal of Clinical Oncology (2024)

9022 Background: High quality education is crucial for hematology/oncology (H/O) training and lifelong learning. However, H/O has historically prioritized clinical and research careers over medical education careers. Consequently, few programs support H/O educators. A CoP is a group that shares “a concern or passion for something they do and learn how to do it better as they interact regularly.” We formed the ASCO Med Ed CoP in 2021 to provide a collaborative network and professional development venue for H/O educators. Methods: Following a published framework for developing a global health professions educator community (Establish-Grow-Sustain), we (ASCO Education Scholars Program graduates) developed CoP mission and vision statements and a leadership structure (Establish), formed committees and projects (Grow), and gathered at the ASCO Annual Meeting and via virtual Town Halls (Sustain). In 2023, we collected demographics and evaluated the CoP using a logic model focused on inputs, activities, outputs, and impact. Results: As of December 2023, the CoP includes 238 members from 143 institutions (38 [27%] non-U.S.): 207 (87%) ASCO members; 127 (53%) women, 106 (45%) men, 5 (2%) no response (NR); 111 (47%) White, 88 (37%) Asian/Pacific Islander, 27 (11%) Latinx/Hispanic, 12 (5%) Black/African-American, 8 (3%) Middle Eastern, 1 (0.4%) African, 16 (7%) NR; 146 (61%) hematologist/oncologists, 68 (29%) trainees, 6 (3%) radiation oncologists, 3 (1%) surgical oncologists, and 15 (6%) other professionals. The logic model is displayed (Table). Conclusions: The CoP has had an impact on its members, ASCO, and beyond and continues to grow and sustain itself by recruiting broadly, driving projects forward, and making structural adjustments for long-term sustainability. Upcoming projects include providing more educational resources and measuring outcomes such as changes in members’ knowledge, skills, and attitudes. Membership diversity continues to be a challenge and a priority. [Table: see text]
Bevacizumab in combination with chemotherapy for treating patients with advanced RET+ non-small cell lung cancer.
Authors: Mihaela Aldea, Arianna Marinello, Isabelle Monnet, Hortense de Saint Basile, Sophie Cousin, Michaël Duruisseaux, Antonio Calles, Giulio Metro, Jon Zugazagoitia, Giacomo Massa, Patricia Gomez, Fabrizio Tabbò, Alessandro Russo, Vincent Fallet, Colin R Lindsay, Emilio Bria, Anna Eisert, Florian Guisier, David Planchard, Benjamin Besse
Journal: Journal of Clinical Oncology (2024)

8647 Background: RET inhibitors (RETi) are currently the preferred first-line treatment in advanced RET fusion-positive (RET+) non-small cell lung cancer (NSCLC). Despite impressive efficacy of RETi, resistance is inevitable, and the optimal therapy beyond RETi remains unclear. Immunotherapy has shown limited efficacy in these patients. This study aims to investigate the impact of adding bevacizumab to chemotherapy regimens on treatment outcomes. Methods: This multicenter, retrospective study included patients with RET+ advanced NSCLC who received either a platinum-doublet chemotherapy (D) (+/-anti-PD-L(1) agents (ICB)) or a non-platinum monotherapy (M), with or without bevacizumab (Bev). Non-platinum agents were limited to pemetrexed, paclitaxel, or docetaxel. Only the first administration of the regimen was considered. Objective responses (OR), progression-free survival (PFS), and overall survival (OS) from the start of treatment were compared between patients receiving and not receiving Bev. Results: Of 185 patients, 20 received Bev in doublet chemotherapy (D+Bev, none with ICB) and 165 did not (D, 68 with ICB). Additionally, 40 underwent single-agent chemotherapy, with 8 on Bev (M+Bev) and 32 without (M). D+Bev patients were younger (median age: 54 vs. 61 years, p=0.026), less often treated with RETi (55% vs. 79%, p=0.023), with no other demographic or disease-related group differences. Both D+Bev and D had a median of 1 treatment line [IQR 1-1]. M+Bev and M had a median of 3 and 2 treatment lines, respectively (p=0.3), and numerically more M+Bev patients had brain metastases (25% vs. 13%, p=0.6). In the D+Bev vs D (+/-ICB) comparison, the OR was 55% vs 47% (p=0.7), and the median PFS was significantly longer in the D+Bev group (17 months vs. 8.8 months, p=0.018). When comparing D+Bev with D+ICB, D+Bev still showed a significant advantage in median PFS (17 months vs 9.7 months, p=0.05). The median OS was 51.4 months for D+Bev compared to 38.7 months for D (p=0.89). Multivariate analysis revealed that Bev use was independently associated with longer PFS (hazard ratio [HR] 0.4, p=0.01), while ECOG&gt;1 (HR 4.3, p&lt;0.0001) and male sex (HR 1.7, p=0.01) were associated with shorter PFS. In the M+Bev versus M group, the OR was 13% versus 25% (p=0.6), median PFS was 2.4 months versus 4.1 months (p=0.06), and median OS was 12.1 months versus 39 months (p=0.06). Conclusions: Bevacizumab with platinum-doublet chemotherapy seems to outperform platinum-doublet with or without ICB in progression-free survival. Prospective research is needed to evaluate the extent of bevacizumab's benefit for RET+ NSCLC.
Survey of actionable driver mutations KRAS and EGFR in non–small cell lung cancer to evaluate coexisting splicing gene and pathway mutations: A CBioportal database analysis.
Authors: Zhaohui Arter, Misako Nagasaka, Sai-Hong Ignatius Ou
Journal: Journal of Clinical Oncology (2024)

8561 Background: Molecularly targeted therapies have advanced treatment for certain cancers, such as lung cancer with specific EGFR or KRAS mutations. However, oftentimes the tumor becomes eventually treatment resistant. This may be partly because cancers driven by EGFR/KRAS mutations may also harbor additional co-occurring genetic alterations. In non-small cell lung cancer (NSCLC), aberrations in RNA splicing pathways have shown substantial implications for tumor behavior and therapeutic responsiveness. Our study focuses on elucidating the interplay between RNA splicing defects and prominent NSCLC mutations. Methods: In this retrospective, cross-sectional study, we analyzed data from 20,719 NSCLC patients enrolled in participating institutions between 2017 and 2022. The data were sourced from the American Association for Cancer Research Genomics Evidence Neoplasia Information Exchange (version 13.0). EGFR L858R, EGFR E746_750del, KRAS G12C, KRAS G12D and other KRAS G12 mutations cases were identified and individually analyzed to abstract co-occurring RNA splicing genomic alterations. Results: Among 20,719 patients with NSCLC, we identified 1309 patients with EGFR L 858R mutation, 1121 patients with EGFR E746_750del mutation, 2446 with KRAS 12C, 852 with KRAS G12D, 1107 with KRAS G12V, 452 with KRAS G12A, 173 with KRAS G12F, and 109 with KRAS G12S. RBM 10 was the most common co-occurring RNA splicing gene for EGFR L 858R (178, 13.6%), followed by CDK12 (31, 2.3%) and SPEN (27, 2 %). Similarly, the most prevalent co-occurring RNA splicing genes with EGFR E746_750del were RBM 10 (38, 3.4%) and SPEN (23, 2 %). RBM 10 was the most prevalent co-existing RNA splicing gene for KRAS G12C (211, 8.6 %), KRAS G12D (63, 7.4 %), KRAS G12V (80, 7.2%), KRAS G12A (59, 13.1%), KRAS G12F (12, 7.0%), KRAS G12S (11, 10.1%) and KRAS G12R (6, 8%). Conclusions: Our study uncovers a crucial link between EGFR and KRAS mutations in NSCLC and RNA splicing gene dysregulation, particularly involving RBM10. Further research in this field is warranted as targeting RNA splicing, alone or alongside existing targeted inhibitors, could substantially enhance treatment efficacy for EGFR+ or KRAS+ NSCLC patients. [Table: see text]
Socioeconomic disparities in survival outcomes of patients with NSCLC with brain metastases: A real-world analysis.
Authors: Shreyas S Bellur, Shahzaib Ahmad, Vivek Bhat, Mohammad Arfat Ganiyani, Ahmad Ozair, Diya Jayram, Atulya Aman Khosla, Vivek Podder, Manmeet Singh Ahluwalia
Journal: Journal of Clinical Oncology (2024)

8569 Background: Racial and ethnic disparities have been previously reported in outcomes of metastatic cancer patients. While novel therapies have improved outcomes of NSCLC patients with brain metastases (BM), however, barriers to therapy persist, warranting updated evaluations of socioeconomic disparities in clinical outcomes. Methods: A retrospective cohort study was conducted on patients diagnosed with NSCLC BM in 2018-2020 in the National Cancer Database. Patients were classified as White, Black, American Indian, Aleutian or Pacific Islander (AAPI), or Asian. Sociodemographic and clinical outcomes were analyzed and reported using median overall survival (mOS) (95% CI). Multivariate analyses were performed using Cox proportional hazard models adjusting for sex, race, facility type, and income and reported using hazard ratios for death (HR) (95% CI). Results: 13850 patients with NSCLC BM were included: 81% (N=11123) were White, 14% (N=1914) Black, 0.5% (N=73) AAPI, 3.7% (N=508) Asian. 8% were treated in community cancer centers (CCC) and 39% in comprehensive CCCs (CCCC). 55% were Medicare-insured and 30% had annual income &gt;$74063. Compared to White, Asian patients had significantly better mOS of 29.1 months (24.57-36.5). Compared to non-Hispanic, Hispanic patients had significantly better mOS at 18.1 months (14.5-24.3). Medicaid and Medicare-insured had significantly worse outcomes vs. private-insured patients – mOS of 14.62 months (12.75-16.49) and 8.84 months (8.41-9.36) vs. 21.72 months (20.37-23.29). In multivariate analyses, compared to White, Asians had an HR of 0.61 (0.53-0.70). Hispanic had a HR of 0.77 (0.67-0.88) compared to non-Hispanic patients (P&lt;0.05). Compared to academic centers, patients treated at CCC (HR 1.42 (1.29-1.57)) and CCCC (HR 1.25 (1.19, 1.32)) had worse outcomes. Patients with higher annual income (&gt;$74063) had better outcomes compared to those with low income (&lt;$46277) (HR 0.83 (0.78-0.89), P&lt;0.002). Conclusions: Asian and Hispanic patients with NSCLC BM had better 3-year survival compared to White and non-Hispanic patients, respectively. Patients at community centers had worse outcomes than those at academic centers. Medicare-insured and Medicaid-insured patients had unfavorable outcomes. Targeted efforts are warranted to improve disparities in outcomes across racial and ethnic groups. [Table: see text]