tbuckley/cabot-search huggingface dataset:
Impact of Hispanic ethnicity on immunotherapy outcomes in hepatocellular carcinoma: Insights from the National Cancer Database.
Authors: Sumit Gaur, Alok Kumar Dwivedi, Ana Eiring, Ioannis Konstantinidis, Rabia Rukhsan, Vishwajeet Singh
Journal: Journal of Clinical Oncology (2024)

438 Background: Hepatocellular carcinoma (HCC) is the fastest-growing cancer in the US with more age-adjusted incident cases in Hispanics compared to non-Hispanics. Immunotherapies are considered integral part of treatment for most unresectable HCC. Recent multinational phase III trials suggest the benefit of immunotherapies may differ based on geographic region and underlying etiology of HCC. We hypothesized that Hispanic ethnicity might influence responses to immunotherapy in HCC. Methods: We analyzed the National Cancer Database (NCDB) to assess the impact of immunotherapy on overall survival (OS) in Hispanic patients with HCC. The database was queried for liver cancer from 2004 to 2020. Kaplan Meier method was used to assess OS and a log-rank test was used to compare survival distribution between Hispanic and non-Hispanic groups. Cox regression analysis was performed to estimate the adjusted effect of ethnicity on OS based on immunotherapy status. NCDB is a joint project of the Commission on Cancer (CoC) of the American College of Surgeons and the American Cancer Society. The CoC's NCDB and the hospitals participating in the CoCÕs NCDB are the source of the de-identified data used herein. Results: A total of 225079 patients were identified of whom 2036 patients (0.9%) received immunotherapy as first-line treatment. Patients with non-Hispanic ethnicity, male sex, who received treatment at academic/research institutions, and were insured were more likely to receive immunotherapy. In the entire cohort, there was no difference (p=0.94) in survival between those who did not receive immunotherapy (median OS,11.63 months; IQR: 2.79, 34.83) vs. those who did (median OS, 10.68 months, IQR: 5.19, 23.29[DA2]). There were more Hispanics in the cohort who did not receive immunotherapy (12.28% vs. 10.61%). In the adjusted Cox analysis, Hispanics had a reduced risk of death than non-Hispanics among patients who did not receive immunotherapy (HR: 0.873, 95%CI, 0.858-0.889; p&lt;0.001). Among patients with immunotherapy, there was no OS difference between ethnicities (HR 0.904, 95% CI, 0.755-1.082; p 0.271). Conclusions: Hispanics were less likely to receive immunotherapy than non-Hispanics. Although Hispanics had a better OS than non-Hispanics among patients without immunotherapy, the differences no longer persist among patients who received immunotherapy. These findings suggest that Hispanic ethnicity may influence responses to immunotherapy. As compared to non-Hispanic whites, Hispanics with HCC have significantly more nonalcoholic fatty liver disease and alcohol-related liver disease as contributing factors. A better understanding of the impact of immunotherapies on alcoholic and nonalcoholic liver disease-related HCC is needed.
Inpatient outcomes of metastatic epidural spinal cord compression in patients with gastric cancer compared to patients with other solid cancer.
Authors: Ayobami Gbenga Olafimihan, Ekrem Turk, Alejandro Nieto Dominguez, Chun-Wei Pan, Chidiebele Omaliko, Muhammad Bilal Ibrahim, Elvis Obomanu, Praise Fawehinmi, Kunnal Batra
Journal: Journal of Clinical Oncology (2024)

255 Background: Metastatic epidural spinal cord compression (MESCC) is an oncologic emergency which can be associated with poor outcomes for cancer patients. Our aim was to study the differences in outcomes of MESCC in patients with gastric cancer (GC-MESCC) compared to those with other solid malignancies. Methods: Healthcare Cost and Utilization Project-Nationwide Inpatient Sample database (2016-2020) was queried to identify all solid (breast, prostate, lung, gastrointestinal, renal and thyroid) cancer patients admitted with spinal cord compression. Multivariate logistic regression was used to evaluate differences in socio-demographics, medical comorbidities and outcomes between MESCC in gastric cancer patients and those with other solid cancers. The primary outcome included inpatient mortality, length of stay (LOS), and total hospital charges (THC). Results: 78,385 patients with the above solid cancers were admitted for spinal cord compression. Among them, 710 had gastric cancer. Patients with gastric cancer were younger (Mean age: 59.1 vs 66.3 years, p &lt; 0.001). They had higher prevalence of anemia (56 vs 41%), protein energy malnutrition (28.9 vs 18.9%, p &lt; 0.001), and lower prevalence of COPD (8.45 vs 18.5%, p =0.003), smoking (22.5 vs 33.6%, p =0.007) and CKD (9.4 vs 12.3%, p =0.03). On multivariate regression, those with GC-MESCC had two-fold higher odds of all-cause mortality (adjusted odds ratio (aOR): 2.0; 95% CI: 1.05-3.96, p = 0.034). On subgroup analysis, mortality was about four times higher for females with GC-MESCC relative to the other group (aOR = 3.8, 95% CI: 1.69-8.52, p = 0.001). There was a trend towards increased LOS (8.9 vs 7.8 days) and THC ($115, 805 vs $96, 074) but it was not statistically significant. Compared with the other cohort, GC-MESCC patients had higher rates of blood transfusion (16.2 vs 9%, p = 0.003). Conclusions: Metastatic epidural spinal cord compression is associated with increased odds of inpatient mortality in gastric cancer patients compared to those with other solid malignancies. Hence, these patients ought to have urgent intervention and close monitoring to prevent adverse outcomes. [Table: see text]
Real world (RW) use and outcomes of regorafenib (REG) flexible dosing in patients (pts) with metastatic colorectal cancer (mCRC) in Europe.
Authors: Marc Peeters, Benoist Chibaudel, Afsaneh Barzi, Helene Ostojic, Xiaoyun Pan, Marie Yasuda, Chi-Chang Chen, Jasjit Multani, Vicky Casey, Zdravko Vassilev
Journal: Journal of Clinical Oncology (2024)

47 Background: In the phase 2 ReDOS study, REG first-cycle dose-escalation showed comparable activity and lower incidence of adverse events in pts with mCRC vs standard dosing. This retrospective cohort analysis aimed to examine RW dosing patterns of REG and associated duration of treatment (DoT) in pts with mCRC in Europe. Methods: Data from pts with mCRC, aged ≥18 years who initiated REG monotherapy from January 1, 2019 to April 30, 2022, were collected retrospectively from chart review by physicians recruited from the IQVIA OneKey database. Pts were categorized by dosing regimen to either flexible dosing regimens (ReDOS-like [&lt;160 mg starting dose] or dose-adjusted [160 mg starting dose with dose adjustments during treatment]) or a standard dosing regimen (160 mg throughout treatment). Results: Overall, 355 pts (France, n=146; Italy, n=143; Belgium, n=66; 68% male, 54% aged ≥65 years) were eligible for inclusion. Nearly half (49%) received a ReDOS-like regimen, 32% received a standard dosing regimen, and 19% received a dose-adjusted regimen (Table). A higher proportion of pts on a dose-adjusted regimen had ≥3 metastatic sites (64% vs 43% for standard dosing) and most had initiated ≥3 REG cycles (93% vs 67% and 64% for ReDOS-like and standard dosing regimens, respectively). Pts receiving a ReDOS-like dosing regimen had worse performance status (ECOG PS ≥2, 35% vs 30% for dose-adjusted and standard dosing) and a higher proportion of KRAS (42% vs 37% and 30% for dose-adjusted and standard dosing regimens, respectively) or NRAS (28% vs 24% and 21% for dose-adjusted and standard dosing regimens, respectively) mutations. Median DoT was longer for ReDOS-like and dose-adjusted regimens vs standard dosing (1.4 and 1.9 vs 1.0 months, respectively; Table). Conclusions: Pts receiving REG flexible dosing regimens (ReDOS-like, dose-adjusted) had longer DoT compared with a standard dosing regimen despite having a higher frequency of adverse prognostic factors. Thus, this study affirms that flexible dosing strategies are viable options for optimizing REG treatment and outcomes in pts with mCRC. [Table: see text]
Real-world assessment of capecitabine and oxaliplatin (CAPOX) tolerability in patients with localized colorectal cancer undergoing curative-intent therapy: A comprehensive single institution analysis.
Authors: Veronica Mears, Nikolas Naleid, Hanna Kakish, J. Eva Selfridge, Madison Conces, Melissa Amy Lumish, David L Bajor, Amit Mahipal, Sakti Chakrabarti
Journal: Journal of Clinical Oncology (2024)

90 Background: The combination of capecitabine and oxaliplatin (CAPOX) is commonly used in patients with localized colorectal cancer (CRC) receiving curative-intent treatment. However, real-world data on the tolerability of CAPOX in this patient population are limited. This study aimed to assess the tolerability of CAPOX in a single-institution cohort of patients with localized CRC. Methods: A retrospective analysis was conducted using our institutional pharmacy database to identify patients with localized CRC who received neoadjuvant or adjuvant CAPOX. Demographic information, clinical characteristics, and treatment details were extracted from electronic health records. The primary endpoint was the rate of treatment completion, defined as the receipt of all planned chemotherapy cycles at full dosage, for both the overall cohort and patients aged 65 and above. Secondary outcome measures included the rate of grade 3 or higher adverse events, the frequency of hospital admissions due to CAPOX-related toxicities, and dose reductions. Results: A total of 153 patients were included in the analysis, with a median age of 61 years (range 32-84). Among them, 49% were female, 78.4% had stage III CRC, and the remaining had stage II disease. The racial distribution was 81% White and 15.7% Black. The proportion of patients who completed all planned CAPOX doses was 55.5% (85/153) in the entire cohort and 38% (23/60) in patients aged 65 and above (p = 0.22). Among patients intended to receive 4 cycles of CAPOX, only 57% (37/65) completed all 4 cycles. Female patients were less likely to complete treatment than male patients (p = 0.01). Dose reductions for oxaliplatin and capecitabine were observed in 37% (57/153) and 39% (59/153) of patients, respectively. Hospitalizations related to CAPOX-induced toxicities occurred in 18% (27/153) of patients, and 31% (47/153) experienced grade 3 or higher adverse events. A switch to FOLFOX was observed in 5% (8/153) of patients. Conclusions: This study highlights that a substantial number of patients with localized CRC undergoing curative-intent treatment with CAPOX do not complete the planned courses, potentially impacting their overall survival. Moreover, a significant proportion of patients experience grade 3 or higher toxicities with CAPOX, necessitating hospital admissions. These findings underscore the need for careful patient selection and management strategies to optimize the therapeutic benefits of CAPOX in this setting.
Efficacy and safety of nivolumab and CapeOX in patients with previously untreated FGFR2-positive, PD-L1-positive advanced gastric cancer: A single-arm, multicenter, phase 2 study NIVOFGFR2.
Authors: Ilya Tsimafeyeu, Gunel Musayeva, Mahmudova Samira, Nana Otkhozoria, Bahadur Abbasov, Alisher Kahharov
Journal: Journal of Clinical Oncology (2024)

303 Background: Nivolumab in combination with chemotherapy has been approved in the first-line treatment of PD-L1-positive metastatic gastric cancer (GC). Fibroblast growth factor receptor 2 (FGFR2) is overexpressed in 30% of patients with GC and is a potential new target for targeted therapy with monoclonal antibodies 1 or allosteric extracellular inhibitors. 2 The aim of the NIVOFGFR2 study was to evaluate the preliminary efficacy of nivolumab in metastatic GC co-expressing PD-L1 and FGFR2. Methods: In this single-arm, multi-center, phase 2 study, eligible patients had metastatic untreated HER2-negative gastric adenocarcinoma with centrally confirmed expression of PD-L1 (CPS≥5; DAKO 28-8) and FGFR2 (moderate (2+) and strong (3+) membranous staining in more than 1% of tumor cells; Abсam EPR24075-418). Patients received nivolumab 360 mg with CapeOX (capecitabine and oxaliplatin) every 3 weeks. The primary endpoint was 1-year progression-free survival (PFS). Secondary endpoints included median PFS and overall survival (OS), objective response rate (ORR) and Grade ≥3 adverse events rate. Results: Seventy-four HER2-negative patients were screened and23 (31%) patients were enrolled (median age 61 years, men 74%, Caucasian 91%, ECOG PS 1-2 78%, organs with ≥2 metastases 78%; CPS (5-9) 22%, (≥10) 78%). 1-year PFS rate was 30,4%. The median PFS was 6.2 months (95% CI 4.4-7.6). The ORR was 21.7% with 1 complete response. With a median follow-up of 11.8 months at data cutoff, the median OS was not reached. Grade ≥3 treatment-related adverse events were reported in 9 (39.1%) patients. Conclusions: An interim analysis demonstrates modest efficacy and an acceptable safety profile of nivolumab in combination with chemotherapy in patients with FGFR2-positive, PD-L1-positive metastatic GC. Further follow-up is ongoing. 1. Wainberg, Lancet Oncol. 2022. 2. Tsimafeyeu, Invest New Drugs. 2023. Clinical trial information: NCT05859477 .
Preliminary results of ALTER-H006: A phase II study of TQB2450 plus anlotinib as adjuvant therapy in hepatocellular carcinoma (HCC) with high risk of recurrence after radical resection.
Authors: Xianhai Mao, Xiaohui Duan, Dongde Wu, Cuncai Zhou, Yifeng Tian, Jian Shen, Guohui Xu, Jianlin Lai
Journal: Journal of Clinical Oncology (2024)

494 Background: Hepatocellular carcinoma (HCC) is one of the leading causes of cancer-related death. Surgical resection remains as the mainstay of curative treatment option, However, the recurrence rate after surgical resection could be high especially in patients with CNLC stage IIb (tumor number ≥ 4) and IIIa (vascular invasion). Herein we evaluated the efficacy and safety of the anti-angiogenic tyrosine kinase inhibitor, anlotinib, plus TQB2450, a novel programmed death-ligand 1 (PD-L1) inhibitor as an adjuvant treatment for HCC with high risk of recurrence after radical resection. Methods: This prospective, multiple-center, single-arm phase II study (NCT05111366) enrolled histologically confirmed resectable HCC pts for CNLC Stage IIb/IIIa with any of the following high-risk factors for recurrence: a) tumor nodules ≥4; b) portal vein tumor thrombus (PVTT): vp1 or vp2; c) hepatic vein tumor thrombus (HVTT): vv1 or vv2. At 4-8 weeks after R0 resection, adjuvant therapy was started with anlotinib (12 mg, p.o., qd, d1-14, q3w) plus TQB2450 (1200 mg, i.v., d1, q3w) until disease recurrence or unacceptable toxicity or up to 18 cycles (~1 year). Primary endpoint was 1-year recurrence-free survival (RFS) rate; secondary endpoints were RFS, 1-year overall survival (OS) rate, and safety. Results: Between January 2022 and August 2023, a total of 22 pts from 4 centers were enrolled, 21 pts included in per-protocol set analysis. The 21 pts were predominantly male (95 %, n = 20), and the median age was 50 years (range: 33–75). Eight pts (38%) had CNLC Stage IIb and 13(62%) had CNLC Stage IIIa HCC. Among them, 19 pts received at least once tumor assessment. According to RECIST 1.1, out of 21 pts, 16 showed no recurrence, 3 relapsed, 1 dropped out and 1 discontinued due to serious adverse events. The 1-year RFS rate was 62.31%（95%CI: 17.15-88.08）, while the median RFS was not mature. Additionally, safety profile exhibited that the regimen was tolerable. 16 of 22 pts (73%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 6 pts (27 %) including hypertension (13.5 %), neutropenia (9 %), and bleeding (4.5 %). Conclusions: The present study indicated that anlotinib plus TQB2450 as adjuvant treatment for HCC with high risk of recurrence after radical resection exhibited potential efficacy and tolerable safety profile. The conclusion should be validated in more participants included subsequently. Clinical trial information: NCT05111366 .
Subgroup analyses of the phase 3 CAIRO3 trial: Association of number and total volume of metastases on survival in patients with metastatic colorectal cancer based on a deep-learning automatic segmentation model.
Authors: Koen Zwart, Michiel J. Zeeuw, Bertine L. Stehouwer, Dania Al-Toma, Sophie Kurk, Manon N.G.J.A. Braat, Pim A. de Jong, Jan J.W. Lagendijk, Anne M. May, Miriam Koopman, Cornelis J. A. Punt, Geert Kazemier, Guus Bol
Journal: Journal of Clinical Oncology (2024)

130 Background: Maintenance treatment with capecitabine and bevacizumab after capecitabine, oxaliplatin, and bevacizumab therapy in metastatic colorectal cancer (mCRC) is shown to be effective with observation as an acceptable alternative. Metastatic burden might aid in shared decision-making and the aim of this exploratory analysis is to assess the prognostic and predictive value of number and total volume of metastases in mCRC patients included in the CAIRO3 study. Methods: Patients in the CAIRO3 study with liver and/or lung metastases were included. Every individual liver and lung metastasis was counted and volumes were assessed using deep-learning automatic segmentation software (SAS analytical platform and Philips IntelliSpace). Lymph node metastases were counted manually. Each scan was supervised by a dedicated radiologist. Kaplan-Meier analyses were used to estimate progression-free survival (PFS) and overall survival (OS) using log-rank testing for statistical comparison. Hazard ratios (HR) were estimated using Cox regression models. Results: A total of 156 patients were included with 154 OS events, in which 8198 metastases were identified: 5179 were liver metastases, 2835 lung metastases, and 184 lymph node metastases. Patients had a mean age of 63 years and 67% were male. At randomization, the median number of metastases was 9 and mean total metastatic volume was 116 cm 3 . Median OS for patients with ≤10 versus &gt;10 metastases was 22.0 months (95%CI: 19.3-29.3) and 14.3 months (95% CI: 11.6-20.9, p-value &lt;0.01), with similar differences for low/high tumor volume. In multivariable analysis number and total volume were independent prognostic markers for PFS and OS, respectively, after adjustment for age, sex, WHO performance score, treatment arm, serum lactate dehydrogenase (LDH) level, site of primary tumor, time to metastases, and treatment response. Benefit of maintenance therapy was most pronounced in patients with ≤10 compared to &gt;10 metastases with a PFS HR of 0.24 (0.12-0.46) compared to 0.52 (0.28-0.96) and OS HR of 0.75 (0.42-1.34) compared to 1.17 (0.66-2.08), demonstrating potential predictive value. Conclusions: Metastatic burden is associated with a poor prognosis in patients with mCRC. Furthermore, patients with limited metastatic disease (1-10 metastases) benefit most from maintenance treatment and this could potentially be a predictive biomarker. [Table: see text]
Safety and efficacy of chemotherapy for patients with unresectable pancreatic cancer concomitant with collagen disease: A multicenter retrospective observational study.
Authors: Hiroyuki Asama, Hiroyuki Okuyama, Yasuyuki Kawamoto, Kumiko Umemoto, Takuo Yamai, Satoshi Kobayashi, Masafumi Watanabe, Yasuo Hamamoto, Takaaki Furukawa, Yohei Kitano, Masayo Motoya, Yuko Suzuki, Akihiro Ohba, Kazuo Watanabe, Naohiro Okano, Kazuhiko Shioji, Noritoshi Kobayashi, Hiroshi Imaoka, Takeshi Terashima, Makoto Ueno
Journal: Journal of Clinical Oncology (2024)

650 Background: In patients with collagen disease, such as rheumatoid arthritis, steroids and immunomodulators are often used for treatment. These treatments increase the risk of adverse events, including infections; thus, cancer patients with collagen disease are often excluded from clinical trials of chemotherapy for cancer. Therefore, evidence is lacking regarding the safety and efficacy of chemotherapy for pancreatic cancer concomitant with collagen diseases. Methods: This was a multicenter, retrospective study in Japan. Patients who started first-line chemotherapy or chemoradiotherapy for unresectable pancreatic cancer between January 2015 and December 2019 and had concurrent collagen diseases were included. We evaluated adverse events (AEs), discontinuation of anticancer treatment due to AEs, progression-free survival (PFS) and overall survival (OS). Results: A total of 52 patients were enrolled from 20 institutions in Japan, and a total of 101 regimens were administered. Concomitant collagen diseases included rheumatoid arthritis (n=35), systemic lupus erythematosus (n=5), Sjögren's syndrome (n=4), vasculitis syndrome (n=3), dermatomyositis/polymyositis (n=2), polymyalgia rheumatica (n=1), systemic sclerosis (n=1), and Behçet’s disease (n=1). The most common regimens for pancreatic cancer were gemcitabine/nab-paclitaxel (GnP, n=40), S-1 monotherapy (n=18), gemcitabine monotherapy (n=15), modified FOLFIRINOX (n=10), S-1 concurrent radiotherapy (n=5), and FOLFOX (n=4). Treatment discontinuation due to AEs occurred in 21 regimens (20.8%). The most common causes of discontinuation were thrombosis in 4 regimens, interstitial lung disease (ILD) in 3 regimens, and fatigue in 3 regimens. Infection as an adverse event was observed in 7 regimens (6.9%). By regimen, GnP had the highest discontinuation rate for adverse events of 37.5% and an incidence of ILD of 15.0%. The median PFS was 5.6 months in first-line therapy, and the median OS was 11.1 months. By regimen, the median PFS (5.8 months) and median OS (13.3 months) for metastatic patients receiving first-line GnP were comparable to those in previous reports on GnP for patients without collagen disease. Conclusions: Patients with pancreatic cancer concomitant with collagen disease have a high discontinuation rate due to AEs, and attention should be given to the occurrence of thrombosis and ILD.