tbuckley/cabot-search huggingface dataset:
Updated results from ALTER-H004 study: Anlotinib combined with TACE as adjuvant therapy in patients with hepatocellular carcinoma (HCC) at high risk of recurrence after surgery—A single arm, multi-center, phase II clinical trial.
Authors: Zheng Wu, Zheng Wang, Lei Zhang, Xiaojing Song
Journal: Journal of Clinical Oncology (2025)

588 Background: High recurrence rate after curative resection significantly compromised the long-term survival of patients with HCC patients (pts). TACE as adjuvant therapy was proved to improve clinical outcomes for pts with high recurrence risk factors after hepatectomy. However, the prognosis of TACE reminded unsatisfactory and controversial. Therefore, this study aimed to identify the efficacy and safety of anlotinib as maintenance adjuvant treatment following inductional TACE in pts with HCC. The preliminary results had been reported in 2024 ASCO GI (Poster 513) and the update results were reported here with longer follow-up duration. Methods: HCC pts with one of the following high risk factors after hepatectomy: ≥5 cm and &lt;10 cm of tumor diameter, tumor number ≥3, tumor microvascular invasion M1 or M2, portal vein tumor thrombus resection (Cheng's classification I/II) were recruited. Eligible pts received cTACE treatment within 1-2 months after hepatectomy, on the 3-5th day after cTACE, oral anlotinib (12mg, qd, d1-d14, q3w) was given until disease recurrence or unacceptable toxicity. The predefined sample size was 30. The primary endpoint was disease free survival (DFS). Secondary endpoints included 1-year DFS rate, time to recurrence and safety. Results: The data cut-off date was April 2024, 29 pts were enrolled and 27 pts received at least once tumor assessment. The median follow-up was 34.1 (IQR, 32.0-40.9) months. Of 27 with assessable efficacy, mDFS was 40.9 (95% CI, 11.4-70.3) months, with 1-, 2-, and 3-year DFS rates of 72.1% (95% CI, 50.2%-85.6%), 63.0% (95% CI, 40.7%-78.9%), and 56.7% (95% CI, 33.6%-74.5%), respectively. 21 of 27 pts (77.8%) experienced treatment-related adverse events (TRAEs). Grade 3 TRAEs occurred in 5 pts (18.5%) included hypertension (7.4%), leukocytopenia (7.4%) and ascites (3.7%), and blood bilirubin increased (3.7%). No grade 4 or 5 TRAEs occurred. Conclusions: Anlotinib combined with TACE as adjuvant therapy in HCC pts at high recurrence risk exhibited encouraging efficacy and tolerable safety profile. And the conclusions needed to be confirmed in large scale clinical trials subsequently. Clinical trial information: NCT04213118 .
Survival benefits of asymptomatic primary tumor resection after bevacizumab plus FOLFIRI as first-line therapy for patients with metastatic colorectal cancer with synchronous unresectable metastasis.
Authors: Hsiang-Lin Tsai
Journal: Journal of Clinical Oncology (2025)

56 Background: Metastatic colorectal cancer (mCRC) poses a clinical challenge and requires a combination of systemic therapy and conversion surgery. Although first-line chemotherapy and target therapy are considered the standard treatments for mCRC, the role of primary tumor resection (PTR) in asymptomatic synchronous mCRC with unresectable metastatic lesion after initial therapy remains relatively underexplored. Methods: A retrospective observational study was conducted from January 2015 to January 2021, involving 74 patients with synchronous mCRC who received bevacizumab plus FOLFIRI as first-line systemic therapy. All 74 patients had unresectable metastatic lesions confirmed through multidisciplinary team (MDT) discussion. Patients' characteristics, PTR data, and radiotherapy (RT) and overall survival (OS) outcomes were analyzed. The patients were categorized into a "PTR" group and a "No PTR" group and then further stratified into IVA, IVB, and IVC subgroups based on the initial mCRC stage. Additionally, four subgroups - namely "PTR(+)/RT(+)", "PTR(+)/RT(-)", "PTR(-)/RT(+)", and "PTR(-)/RT(-)" were formed to assess the combined effects of PTR and RT. Results: The median OS for all the patients was 23.8 months (20.5 - 27.1 months). The "PTR" group exhibited a significantly higher median OS of 25.9 months (21.3 - 30.5 months) compared with 21.4 months (15.8 - 27.1 months) in the "No PTR" group ( P = 0.048). Subgroup analyses revealed a trend of improved survival with PTR in patients with stage IVA and IVB; however, the results were not statistically significant ( P = 0.116 and 0.493, respectively). A subgroup analysis of PTR and RT combinations revealed no significant difference in median OS rates. Conclusions: For asymptomatic mCRC with synchronous unresectable distant metastasis. PTR following first-line therapy with bevacizumab plus FOLFIRI can provide a survival benefit, particularly in stage IVA/IVB patients compared with stage IVC patients. Additionally, RT for primary tumor did not provide an additional OS benefit in mCRC with unresectable metastasis. A prospective randomized trial with a larger sample size is essential to further elucidate the role of PTR in this context.
Assessment of nutritional status in elderly patients with gastroesophageal cancer: A post hoc analysis.
Authors: Jasmeet Kaur, Vanessa Wookey, Caitlin R. Meeker, Meghan Meghan Connors, Elizabeth A. Handorf, Mohamedtaki Abdulaziz Tejani, Grant Richard Williams, Arthur Winer, Sukeshi Patel Arora, Juhi Mittal, Kelly A. Filchner, Namrata Vijayvergia, Efrat Dotan
Journal: Journal of Clinical Oncology (2025)

389 Background: Elderly patients with gastroesophageal cancer (GEC) frequently suffer from malnutrition due to tumor location and treatment-related toxicity. Malnutrition is associated with increased morbidity and mortality in this population. This study investigates the relationship between body mass index (BMI), Mini Nutritional Assessment (MNA) scores, unintentional weight loss (UWL), and chemotherapy toxicity while identifying key factors influencing nutritional status. Methods: This post hoc analysis utilized data from a prospective, multicenter study of patients aged 65 and older with all stages of GEC undergoing chemotherapy. Nutritional assessments were conducted using validated tools, focusing on BMI, MNA, and UWL over three months post enrollment. We defined malnourished patients as those with abnormal BMI (&lt;18.5 or &gt;30), low MNA (0-11), and significant UWL (≥10%). We analyzed associations between nutritional status and geriatric assessment comorbidities, depression score, functional status, cognition, hospitalization, treatment toxicity, and social support using Fisher’s exact tests. Results: Eighty-two patients were enrolled, with a median age of 73 years (range 65-91 years). The cohort was predominantly male (74%) and primarily presented with stage III-IV disease (82%), most receiving first-line therapy (79%). Primary sites included gastric (32%), esophageal (43%), and gastroesophageal junction (26%). Notably, 34% of patients had abnormal BMI, with 2 patients classified as underweight (BMI &lt;18.5) and 19 as obese (BMI &gt;30). Approximately 69% reported UWL, of 10% or greater. MNA scores indicated malnutrition in about 66% of patients (severe (0-7): 15 patients; moderate (8-11): 37 patients), while 31% scored within the normal range (12-14).Hospital admissions were significantly higher in patients with low MNA (33% vs. 3%; p=0.002) and UWL (29% vs. 8%; p=0.047). No significant correlations were observed between nutritional status and treatment type, treatment toxicity, or other geriatric assessment variables, including functional status and social support. Conclusions: MNA and UWL are effective indicators of nutritional status in elderly GEC patients, while BMI is not a reliable measure. Malnutrition significantly correlates with increased hospital admissions, highlighting the need for reliable tools to measure malnutrition to implement necessary interventions. Further research is required to explore the broader implications of malnutrition on treatment outcomes and quality of life in this vulnerable population.
The crossover of the bevacizumab and panitumumab survival curves in the PARADIGM study: A clue to time-related effects of bevacizumab on the risk of tumor progression.
Authors: Dan Aderka, Kei Muro, Takayuki Yoshino
Journal: Journal of Clinical Oncology (2025)

159 Background: The PARADIGM study in CRC patients demonstrated a cross over of the bevacizumab survival curve below the panitumumab survival curve at 28 months, followed by a steady decrease of the bevacizumab survival curve below the panitumumab survival curve up to 11% by 5 years. Similar differences were seen in the FIRE3, CALGB-80405 and PEAK trials starting at 20 months, suggesting an unsuspected time-related effect of bevacizumab on patient’s survival starting at about 2 years after its 1st administration. Methods: Review of time related effects of bevacizumab in 1st and 2nd line trials conducted in CRC, breast, ovary and renal cancer showed a significant PFS but no OS survival benefit, with a detrimental effect on survival in the adjuvant setting (AVANT, NSABP-08 studies). Preclinical data on tumor biology, intratumor-heterogeneity, clonal evolution and the cross talk between bevacizumab and the diverse tumor microenvironments, was correlated to the clinical data, in an attempt to explain the time-related effects of the biological. Results: In the NSABP-08 trial, bevacizumab reduced relapse for 6 months, effect diminished and lost at 12 months. At 24 months after bevacizumab's 1st administration, the relapse of the bevacizumab treated population increased steadily over the control. Identical kinetics were shown in AVANT study and metastatic ovarian patients suggesting that these time-related effects of bevacizumab are universal. The biologic explanation of the clinical data is that short-term treatment with bevacizumab (plus chemotherapy) induces initial tumor stasis and shrinkage, followed by selection and emergence of more aggressive and resistant tumor clones, characterized by an accelerated growth, invasiveness and metastasis shifting the overall tumor growth kinetics to a steeper angle. Bevacizumab appears to be effective for the time of its administration, followed by a slow rebound after its discontinuation. The initial survival benefit will be lost at about 20-24 months after its first administration, as clearly demonstrated in the PARADIGM, FIRE-3, CALGB 80405 and the PEAK studies. Conclusions: As bevacizumab benefit persist for about 2 years after its 1 st administration, it explains the "survival benefit" obtained in studies with with median survival of 20 months but not in studies with survivals &gt;30 mo. (PARADIGM, FIRE-3, CALGB 80405 and the PEAK). This phenomenon also explains the crossover of the survival curves in PARADIGM study and the benefits of bevacizumab obtained preferentially in patients with short survival (rt. sided tumors), high tumor burden, and 2 nd and 3 rd line CRC.
Disparities in incidence and mortality of colorectal cancer in Appalachian Kentucky.
Authors: Lindsay Austin O'Shaughnessy, Kennedy Sabharwal, Chevy Singh, Oscar Garcia, Robert Clell Miller
Journal: Journal of Clinical Oncology (2025)

33 Background: Since the late 1990s, both the incidence and mortality of invasive colorectal cancer (CRC) have decreased across the United States, including in Kentucky. Despite this, CRC incidence and mortality are above national average in Kentucky. Over the last two decades, a disparity in CRC incidence and mortality has emerged between Appalachian Kentucky (AK), a distinct eastern region, and Non-Appalachian Kentucky (NAK). This disparity is attributed to differences in social and structural determinants of health (SSDH) between these populations. Methods: Age-adjusted CRC incidence and mortality rates (2016-2020) for both Kentucky and the U.S. were obtained from the National Cancer Institute’s public database. Data from the Kentucky Cancer Registry were used to compare CRC incidence and mortality rates in AK and NAK counties from 1994-2021. Incidence rate ratio analyses across discrete time periods demonstrated statistical differences between these regions. Results: Compared to national data (2016-2020), Kentucky's CRC age-adjusted incidence and mortality rates were significantly higher: 45.9 vs. 36.5/100,000, 25.8%, for incidence, and 16.2 vs. 13.1/100,000, 23.7%, for mortality (both p&lt;0.0001). From 1995-2003 incidence and 1994-2003 mortality of CRC, were higher in NAK, these rates eventually decreased and equalized between NAK and AK. By 2010-2015 both incidence and mortality rates were higher in AK, 55.8 vs 48/100,000, 16.3%, (p=&lt;0.0001) and 20.1 vs 15.8/100,000, 27.2%, (p=&lt;0.0001) respectively. The most recent data (2016-2021) shows that these significant disparities persist, with AK’s incidence and mortality 51.8 vs 44.1/100,000, 17.5% (p=&lt;0.0001) and mortality 19.0 vs 15.1/100,000, 25.8% (p=&lt;0.0001) higher, respectively. Conclusions: While CRC rates have decreased nationwide and in Kentucky, a pronounced gap in both incidence and mortality has developed between Appalachian and Non-Appalachian Kentucky. Appalachian counties—which are more rural and impoverished—face greater barriers to accessing preventive healthcare, contributing to this disparity. Additionally, AK has higher rates of obesity, poverty, smoking, and lower educational attainment and screening rates . Recent public health efforts, such as promoting stool-based screening and increasing preventive care discussions, aim to reduce these disparities. However, delays in CRC screenings during the COVID-19 pandemic— resulting in approximately 1.7 million missed colonoscopies nationally— may have skewed the most recent data, necessitating further analysis in the coming years.
Galeterone monotherapy in advanced pancreatic ductal adenocarcinoma: Results from a phase two trial.
Authors: Aaron Ciner, Yixing Jiang, Vincent Njar, David J Weber, Margaret Carder
Journal: Journal of Clinical Oncology (2025)

744 Background: Advanced pancreatic ductal adenocarcinoma (PDAC) is a devastating disease with limited treatment options. Dysregulated MAPK and PI3K signaling in PDAC activates the eukaryotic translational initiation complex, promoting cell growth, chemoresistance and metastatic spread (PMID 25593033). Galeterone, a novel steroidal anti-androgen, downregulates critical mediators of this complex including Mnk1/2 and phosphorylated eIF4E, thereby blocking epithelial-to-mesenchymal transition and NF-kB activity. In-vitro, galeterone exhibits anti-tumor activity both alone and in combination with gemcitabine and slows tumor growth in a MiaPaCa-2 xenograft murine model (PMID 28881737). We present results of the monotherapy arm from an ongoing phase two trial evaluating galeterone +/- gemcitabine for patients with advanced PDAC. Methods: Patients with locally advanced or metastatic PDAC, an ECOG performance status of 0-2 and adequate organ function, who progressed on two prior lines of systemic therapy were eligible. Galeterone was administered orally at 2550mg daily and gemcitabine intravenously at 1000mg/m 2 weekly for three weeks on 28-day cycle. The primary endpoint was radiographic response rate per RECIST v1.1 and secondary endpoints included progression-free survival (PFS), overall survival (OS) and safety. We used a Simon’s optimal two-stage design with a null hypothesis of p 0 =0.05 and one-sided alternative of p 1 =0.20 with an early stopping rule for futility in each arm. Due to poor accrual and no signal of activity, the galeterone alone arm closed after enrollment of four patients. Results: Four patients were evaluable for the primary endpoint. Ages ranged from 43 to 68. Two patients were male and two were female. Two patients were white and two were black; one patient was Hispanic/Latino. All patients had ECOG PS of 1. No patients had a radiographic response; the best response was progressive disease (PD). PFS from cycle 1 day 1 ranged from 0.9 – 1.7 months and overall survival between 1.8 – 3.6 months. The only treatment-related adverse events (TRAEs) were grade 1 dizziness and grade 3 fatigue in one patient each. There were no treatment-related serious adverse events. No patients required dose modification or discontinued due to TRAEs. Conclusions: Galeterone showed no clinical activity, but with a favorable safety profile, as a single-agent in heavily pre-treated patients with advanced PDAC. Activation of the Mnk-eIF4E axis mediates chemoresistance in PDAC and galeterone may prove more efficacious with gemcitabine. This combination arm is currently open to enrollment. Clinical trial information: NCT04098081 . Clinical outcomes with galeterone monotherapy in PDAC. Pt # Age Prior lines of Therapy Time on Treatment (days) Best Response PFS (months) OS(months) 1 68 4 46 PD 1.5 3.6 2 59 2 54 PD 1.7 3.8 3 55 2 47 PD 1.4 2 4 43 2 35 PD 0.9 1.8
Prognostic analysis of pathological complete response after neoadjuvant therapy for locally advanced gastric cancer: A national, multicenter, retrospective study.
Authors: Jie Chen, Yingxue Liu, Chao Lin, Lu Zang, Hao Xu, Liang Shang, Zhiyuan Xu, Wei Li, Zhiming Ma, Chunchao Zhu, Ping Li, Weihua Yu, Jiang Yu, Jian Zhang, Yi Cao, Fenglin Liu
Journal: Journal of Clinical Oncology (2025)

346 Background: Several research findings indicate that some patients with locally advanced gastric cancer (LAGC) who undergo neoadjuvant therapy followed by curative surgery can achieve pathological complete response (pCR). Whether pCR is equivalent to cure, serves as a good prognostic indicator for long-term survival, and whether patients achieving pCR require subsequent adjuvant therapy are still unknown. Therefore, we conducted a nationwide multicenter retrospective study to investigate the long-term efficacy of patients with LAGC who achieved pCR after neoadjuvant therapy. Methods: Clinical and pathological data were collected from 351 patients with locally advanced gastric cancer who achieved pCR after neoadjuvant therapy between January 2018 and October 2023 at 14 medical centers in China. These patients were matched 1:1 with non-pCR patients based on age, gender, clinical T stage, and N stage. This study evaluated general clinical data, neoadjuvant treatment regimens, cycles, surgical outcomes, and follow-up information including postoperative adjuvant therapy, recurrence, metastasis, and survival status up to November 2023. Results: Negative Serum tumor markers, non-signet ring cell carcinoma and neoadjuvant treatment regimens were closely associated with pCR. Patients achieving pCR were more likely to reach ypN0 status after neoadjuvant therapy compared to non-pCR patients. Survival analysis showed significantly higher overall survival (OS) and disease-free survival (DFS) in pCR patients compared to matched non-pCR patients. Moreover, OS and DFS were significantly higher in ypN0 patients within the pCR group compared to non-pCR patients. However, there was no significant difference in OS and DFS between ypN+ patients in the pCR group and non-pCR patients. Additionally, postoperative adjuvant chemotherapy did not significantly impact OS and DFS in the pCR group. Conclusions: pCR is an independent prognostic factor for OS and DFS. However, survival benefits from pCR are limited to patients achieving ypT0N0 status, while ypT0N+ patients do not benefit from pCR. Furthermore, adjuvant chemotherapy may not improve the prognosis of patients achieving pCR after neoadjuvant therapy.
Immune checkpoint inhibitors (ICIs) in deficient mismatch repair (dMMR)/microsatellite instability (MSI) non-colorectal cancers: Real world Indian data and the use of alternative dosing.
Authors: Dishant Vaddoriya, Anant Ramaswamy, Vivek Agarwala, Priya Tiwari, Vikas Talreja, Saphalta Baghmar, Shefali Sardana, Vineet Govinda Gupta, Peyush Bajpai, Chandrakanth MV, Vikas S. Ostwal, Shivani Raina, Vallish Shenoy, Prabhat Ghanshyam Bhargava, Viraj Kiran Lavingia
Journal: Journal of Clinical Oncology (2025)

347 Background: Immune checkpoint inhibitors, predominantly pembrolizumab and dostarlimab, have been approved in deficient mismatch repair (dMMR)/ microsatellite instability (MSI) non-colorectal cancers. There is also an emerging data to suggest significant clinical activity for low-dose ICIs (LD-ICIs) in these cancers. Methods: A multi-institutional retrospective analysis in Indian patients with dMMR/MSI-H advanced/metastatic non-colorectal carcinomas treated with ICIs (irrespective of dose or schedule) between 2017 and 2024 was conducted. The primary objective of the study was to evaluate 12-month Overall survival (OS) for the whole cohort as well as LD-ICI and standard dose ICI (SD-ICI) cohorts, while other secondary objectives included assessment of overall response rates (ORR) (assessed by RECIST v1.1 as per local radiological reporting), 12-month progression free survival (PFS) and incidence of immune related adverse events (IRAEs). Results: A total of 51 patients were available for analysis. The most common tumour types were gastrointestinal (64%, commonly gastric cancer, oesophageal cancer and cholangiocarcinoma) and endometrial cancers (23%). Eighty-four percent of patients received ICI monotherapy, while the remaining 16% received varying combinations of ICIs with chemotherapy and tyrosine kinase inhibitors. Nivolumab was used in 24 patients (47%) while pembrolizumab was used in 17 patients (33%). With a median follow-up of 14 months, 12-month OS was 72% and 12-month PFS was 62% in the entire cohort. The corresponding 12-months OS and 12-month PFS for those receiving SD-ICIs (n=29) was 69% and 62%, while it was 72% and 64%, respectively for the LD-ICIs cohort (n=22). The ORR was 61%, with 10 patients (20%) achieving complete response (CR) and 21 (41%) achieving partial response (PR). The most common IRAEs (all grades) were fatigue (62%), thyroid disturbances (37%), and pruritus (23%). Conclusions: The current study from India highlights the importance of treating non-colorectal dMMR/MSI-H cancers with ICIs and shows outcomes commensurate with published trial data. Within the confines of a small retrospective study with a short follow-up, low dose ICIs should be explored in these patients in scenarios where standard dosing schedules are not feasible due to logistic reasons. Key Words – Low dose immunotherapy; non-colorectal dMMR/MSI-H cancers; Overall survival.