tbuckley/cabot-search huggingface dataset:
Real-world (RW) study in patients (pts) with metastatic colorectal cancer (mCRC) with long-term responses to regorafenib in the USA.
Authors: Richard D. Kim, Xiaoyun Pan, Helene Ostojic, Yiqiao Zhang, Orsolya Lunacsek, Federica Pisa, Marc Peeters
Journal: Journal of Clinical Oncology (2024)

48 Background: Anecdotal evidence suggests that some pts with mCRC experience significantly longer responses to REG in clinical care settings, including a case exceeding 9 years. However, comprehensive studies on long-term responders to REG are lacking. We evaluated demographic/clinical characteristics of pts with long-term response (LTR) to REG using duration of treatment (DOT) as a surrogate for treatment response. Methods: This was a retrospective cohort study using the US nationwide de-identified Flatiron Health Electronic Health Record-derived database. The study period was January 1, 2013 to May 31, 2023, and adult pts with mCRC who initiated REG monotherapy (index date) from July 1, 2013 to December 31, 2022 were included. DOT for pts with LTR of ≥5 months (LTR5 [primary objective]; mos) or ≥4 mos (LTR4 [secondary objective]) were determined. Results: A total of2,326 eligible pts (median age 64 yrs; 56% male) had initiated REG during the study period. Overall, 346 pts (15%; median age 65 yrs) had LTR5 and 503 pts (22%; median age 65 yrs) had LTR4. Among pts with LTR5, 46% had stage IV disease at initial diagnosis, 68% had ECOG performance status (ECOG PS) 0‒1 at index, 64% received prior bevacizumab (BEV), and of pts tested at index with results, the median carcinoembryonic antigen (CEA) level was 35 ng/mL, and 51% and 5% had a KRAS and BRAF mutation at index, respectively; pts with LTR4 had similar characteristics (Table). Median time from initial CRC diagnosis to index date was 39.2 mos for pts with LTR5 and 38.6 mos for pts with LTR4. Of pts who initiated REG before 2019 (n = 1,070), 14% had LTR5 and 21% had LTR4; of pts who initiated REG from 2019 onwards (n = 1,256), 16% had LTR5 and 22% had LTR4. Among pts with LTR5, 33% and 23% had received REG as third-line (3L) or fourth-line (4L) treatment, respectively; among pts with LTR4, 34% and 23% had received REG as 3L or 4L treatment, respectively. Median time to discontinuation of REG was 7.3 (95% CI 6.9, 7.8) mos in pts with LTR5 and 6.0 (95% CI 5.7, 6.2) mos in pts with LTR4. Median follow-up time (from index date) was 13.3 mos and 11.1 mos in pts with LTR5 and LTR4, respectively. Conclusions: This is the first large-scale RW evidence study to describe demographic/clinical characteristics of pts with LTR to REG. Pts demonstrating LTR typically had favorable ECOG PS at REG initiation, less advanced disease at initial diagnosis, and the majority had received prior BEV. [Table: see text]
Recurrence in the pelvic side wall after lateral lymph node dissection for rectal cancer.
Authors: Misato Takao, Kazushige Kawai, Maki Takagi, Nozomi Funatsu, Soichiro Natsume, Daisuke Nakano, Tatsuro Yamaguchi
Journal: Journal of Clinical Oncology (2024)

49 Background: Locally advanced rectal cancer poses a persistent challenge due to the risk of local recurrence, which impacts patient outcomes and quality of life. To address this, lateral pelvic lymph node dissection (LPND) has emerged as a surgical approach to improve local control. However, comprehensive studies evaluating the outcomes and patterns of recurrence after LPND are limited. This retrospective study aimed to fill this gap and provide insights into the effectiveness of LPND. Methods: We conducted a retrospective analysis of 515 patients diagnosed with stage II-III lower rectal cancer who underwent TME and LPND between January 2005 and August 2022. Clinicopathological data were collected, and tumor staging followed the TNM classification system. Recurrence patterns, survival rates, and factors influencing lateral pelvic recurrence were assessed. Results: In our cohort, 18.8% of patients had pathologically positive lateral lymph nodes. Patients with lateral lymph node metastasis exhibited significantly lower 5-year relapse-free survival (31.6%) and overall survival (47.8%) rates compared to those without metastasis (69.5% and 84.7%, respectively). Local recurrence occurred in 20.1% of all patients, with 6.7% experiencing lateral pelvis recurrence (LPR) and 17.4% central pelvis recurrence. Multivariate analysis identified age over 75, lateral lymph node metastasis, and adjuvant chemotherapy as independent risk factors for LPR. Conclusions: Lateral pelvic lymph node dissection remains a valuable tool in managing locally advanced rectal cancer. Our findings underscore the importance of surgeon expertise in performing LPND and the potential benefits of combining treatments to further reduce lateral recurrence. LPND should continue to be explored and refined to enhance patient outcomes in this challenging clinical scenario.
Maintenance therapy with olaparib or selumetinib plus durvalumab (S+D) according to genetic profile of metastatic pancreatic adenocarcinoma (m-PDAC) controlled with modified FOLFIRINOX (mFFX): A phase II randomized MAZEPPA GERCOR D19-02 PRODIGE-72 study.
Authors: Pascal Hammel, Meher Ben Abdelghani, Gael Roth, Ayhan Ulusakarya, François Ghiringhelli, Clemence Toullec, Christophe Borg, Olivia Hentic Dhome, Isabelle Trouilloud, Laetitia Dahan, Sandrine Hiret, Olivier Bouche, Yves Rinaldi, Jean-Frédéric Blanc, Christelle De La Fouchardiere, Cindy Neuzillet, Maud Kamal, Antoine Falcoz, Anthony Turpin, Rosine Guimbaud
Journal: Journal of Clinical Oncology (2024)

673 Background: Maintenance treatments in m-PDAC patients (pts) after FFX induction is discussed. We assessed the efficacy of genetic-driven maintenance in pts with controlled disease. Methods: In this multicenter, open-label, phase II study, PS 0-1 pts with histologically confirmed m-PDAC controlled after 4 months (mo) of mFFX received a genetically-driven maintenance therapy (centralized analysis): BRCAness - olaparib 300 mgx2/d (Arm A); no BRCAness, but KRAS mutation - randomization (2:1) to S+D (1500 mg IV q4w + 75 mg PO BID; Arm B) or FOLFIRI q2w (Arm C), until confirmed progression or toxicity. Statistical hypotheses: Arm A, PFS4mo rate after inclusion - H0: PFS4mo ≤40%, H1: PFS4mo ≥70%; Arm B and C, H0: PFS c =PFS b , H1: PFS c &lt;PFS b (one-sided 2.5% α-type I-error and 10% β-type 2). A prespecified single interim analysis for futility using a-spending function with O’Brien-Fleming boundaries was planned after 33.1% of events (~93 pts). The Kaplan-Meier method and a swimmer plot were applied. Results: 124 pts were included in the study; Arm A: 16 pts (male: 9, median age: 67 years, PS 0: 9 pts) received olaparib; PFS 4mo: 50%; median PFS: 3.7 mo (1.7-9.4), ORR: 13%, median OS: 18 mo (5.5-21.5). Arm B/Arm C: at interim analysis (12/5/2022): 104 pts were randomized (Arm B/Arm C: 70/34); median PFS in Arms B and C: 3.5 mo (95% CI 2.1-3.9) vs 5.7 mo (95% CI 2.2-10.7), respectively. Due to futility, inclusions were stopped. At final analysis (data cutoff: 06/15/2023) with median follow up of 11.2 mo (95% Cl 9.4-13.1): 108 pts (male: 53%, age: 63.5 years, PS 0: 44%) were treated (Arm B/Arm C: 72/36). 123/124 pts (ITT population) had ≥1 cycle treatment (median: 4.0 [IQR, 2.0-6.0]). Primary endpoint was not met: median PFS 3.7 mo (95% Cl 2.1-5.0) in Arm B vs 6.6 mo in Arm C (95% Cl 2.6-8.7); HR=1.6 (0.99-2.58), P=0.0523. Median OS (entire population): 12.7 mo (95% CI 8.7-18.2); 10.1 mo (95% CI 8.3-20.6) in Arm B and 17.3 mo (95% CI 8.4-20.9) in Arm C. The toxicity profile: ≥1 grade 3-4 treatment-related arms (A/B/C) was as expected: 18.8%, 23.6%, 28.6% of pts. Conclusions: MAZEPPA study did not meet its primary endpoint of improving PFS4mo in m-PDAC pts treated with S+D maintenance vs those receiving FOLFIRI. Data on genomic alterations analyses will be presented at the congress. Clinical trial information: NCT04348045 .
Prognostic value of the timing of immune checkpoint inhibitors infusion in patients with advanced hepatocellular carcinoma.
Authors: Alina Pascale, Marc Antoine Allard, Amal Benamar, Francis Levi, Rene Adam, Olivier Rosmorduc
Journal: Journal of Clinical Oncology (2024)

457 Background: Experimental and clinical data in melanoma and lung cancer suggest that the response to immune checkpoint inhibitors (ICI) may be influenced by circadian rhythms. However, similar findings are lacking in hepatocellular carcinoma (HCC). The aim of this study was to assess the impact of infusion timing of atezolizumab, an ICI, associated or not with bevacizumab, as first line systemic treatment in advanced HCC. Methods: We retrospectively analyzed all consecutive patients, who received, as first line systemic treatment, at least two cycles of atezolizumab +/- bevacizumab for advanced HCC in Paul Brousse Hospital, Villejuif, France, between January 2020 and October 2022. We split them in two groups: 1) patients receiving the first two cycles after 1 pm (afternoon group); 2) patients receiving at least one of the two first cycles before 1 pm (morning or mixed group). Cox regression models were used to assess the prognostic value of ICI infusion timing for the overall survival (OS). Results: A total of 131 patients were analyzed. 119 patients (90.8%) were male, with a median age of 70 years [35; 88]; 40 patients (31%) had performance status (PS) ≥ 1. 103 patients (79%) had cirrhosis; 61 patients (46.6%) had portal hypertension. 49 patients (37.4%) had metastatic HCC and 52 patients (40.6%) had portal vein thrombosis at diagnosis. The mean initial level of alpha-fetoprotein was 5,212.8 ng/mL (SD: 18,681.8). 36 patients (27.5%) received only atezolizumab. 41 patients were included in the first group and were compared to 90 patients included in the second group. There were no significant clinical differences between the two groups. The median OS was significantly lower in the afternoon group compared to the morning or mixed group (11.5 months vs 18.7 months, p = 0.015). In univariate analysis, PS ≥ 1 (p = 0.025), initial level of alpha-fetoprotein (p = 0.030), monotherapy by atezolizumab (p = 0.004) and the first two cycles of ICI infusion after 1 pm (p = 0.018) were significantly correlated with OS. The first two cycles of ICI infusion after 1 pm remains an independent factor significantly associated with OS in the multivariate Cox model, with HR 2.29, 95% CI: 1.27-4.14, p = 0.005 (Table). Conclusions: Our results suggest that the afternoon infusion of the first two cycles of ICI is associated with lower outcomes in patients with advanced HCC, independently of other prognostic factors. There may be confounding factors due to the variability of administration of further perfusions. Larger data are needed to confirm such findings. [Table: see text]
Neoadjuvant SBRT plus regional nodal irradiation with concurrent capecitabine for patients with resectable pancreatic cancer: Survival analysis of prospective phase 1 trial.
Authors: Mustafa Basree, Jacob Witt, Sharon M. Weber, Nataliya Volodymyrivna Uboha, Rebecca Minter, Meghan G. Lubner, Daniel Erik Abbott, Dustin A. Deming, Noelle K. LoConte, Syed Nabeel Zafar, Monica Arun Patel, Sam Joseph Lubner, Jeremy D. Kratz, Mark A. Ritter, Pranshu Mohindra, Michael F. Bassetti
Journal: Journal of Clinical Oncology (2024)

652 Background: Radiation may have a role in management of patients with early-stage pancreatic cancer. However, the role of regional nodal irradiation (RNI) is not well defined despite the high frequency of occult nodal disease. The goal of this trial was to evaluate the safety and feasibility of stereotactic body radiation therapy (SBRT) to primary disease with RNI, combined with capecitabine as a neoadjuvant approach for patients with resectable pancreatic cancer. Updated survival analysis will be presented here. Methods: This is a prospective, single institution, phase IA/B dose-escalation trial that enrolled patients with biopsy-proven, resectable, pancreatic adenocarcinoma between 2014 – 2019 (NCT1918644). Patients were enrolled into one of the 3 cohorts with escalating dose levels. Neoadjuvant SBRT to the primary tumor was delivered in 5 fractions of 5, 6, or 7 Gy with concomitant capecitabine. All patients received RNI 5 Gy x 5 fractions. Our initial report found no dose-limiting toxicities (Witt et al IJROBP 2020). Clinicopathologic features were summarized using descriptive statistics. Kaplan-Meier curves were employed for survival analysis. Results: Seventeen patients were enrolled on the protocol with sixteen evaluable (94.1%). Thirteen (76.5%) patients proceeded to surgery. Median follow up was 31.1 months (2.0 – 73.2). Among the evaluable patients, 63% were male, median age at diagnosis was 73 years (63 – 84), pre-treatment CA 19-9 149.5 U/mL (2.0 – 19358.0). The majority of patients had cT2-3 (94%) and cN0 (87.5%) disease. In patients who underwent resection, median time from radiation to surgery was 19.7 days (14.8 – 42.4), with median of 18 lymph nodes removed (11 – 27). Pathologically involved nodes were present in 69.2% of patients with a median of 2 nodes (1 – 10). Five patients (31.3%) received neoadjuvant chemotherapy, and ten (62.5%) received adjuvant chemotherapy. At the time of data cutoff, median overall survival was 31.1 months (2.3 – 73.6), and median locoregional control and distant metastasis free survivals were 32.8 months (4.0 – 59.5) and 15.3 months (0.4 – 73.6), respectively. No further radiation related toxicities were noted since the prior report. Conclusions: Neoadjuvant chemoradiation with SBRT and capecitabine to primary disease with RNI is feasible and provided a promising signal of durable local control in our study, despite high rates of pathological nodal involvement. Further investigation of this strategy is warranted in a larger cohort of patients. Clinical trial information: NCT1918644 .
Prognostic factors for GEM + nab-PTX combination therapy in elderly patients with pancreatic cancer.
Authors: Kazuki Watabe, Izumi Ohno, Miho Sakai, Tomoya Takahashi, Nana Yamada, Shodai Tohyama, Yu Sekine, Jihei Sugihara, Mayu Ohuchi, Hiroki Nagashima, Koji Takahashi, Kohichiro Okitsu, Motoyasu Kan, Hiroshi Ohyama, Masayuki Ohtsuka, Naoya Kato
Journal: Journal of Clinical Oncology (2024)

678 Background: Japanese Clinical Practice Guidelines for Pancreatic Cancer 2022 recommends gemcitabine (GEM) + nab-paclitaxel (nab-PTX) therapy (GnP regimen) as the first line chemotherapy for elderly patients with pancreatic cancer. In Japan, it is reported that about 69% of pancreatic cancer patients are elderly, and Only few group reported the safety of GnP regimen. In this study, we investigated the anti-tumor efficacy and prognostic factors of GnP regimen in patients with pancreatic cancer at our hospital, with a particular focus on age. Methods: 160 patients who started GnP therapy as the first line treatment for unresectable pancreatic cancer between February 2016 and December 2021 were included in the study. 70 years of age or older was defined as elderly, and patient background and treatment efficacy were compared in two groups: non-elderly patients (n=84) and elderly patients (n=76). Prognostic factors were also compared between the overall population and the elderly. Results: Patients with a primary lesion in the pancreatic head were 32 (38.1%) of the non-elderly patients and 35 (46.1%) of the elderly patients. 60 patients (71.4%) of the non-elderly and 38 (50.0%) of the elderly had distant metastases. The median overall survival was 16.0 months for the non-elderly and 17.7 months for the elderly, with no significant difference (p=0.93). Significant prognostic factors for the overall subject population were ECOG PS (HR 1.80, p=0.019), liver metastasis (HR 2.36, p&lt;0.01), CRP (HR 1.91, p&lt;0.01) and NLR (HR 2.65, p&lt;0.01). The only significant prognostic factor in the elderly was liver metastasis (HR 2.59, p&lt;0.01). Conclusions: GnP regimen in pancreatic cancer can be expected to have the same antitumor effect in elderly patients as in non-elderly patients. However, significant prognostic factors were reduced in the elderly, we need to identify specific factors to determine the indication for treatment in the elderly patients.
Impact of adding nivolumab to first-line chemotherapy in patients with advanced gastric cancer.
Authors: Mai Utsumi, Hiroki Yukami, Dai Okemoto, Toru Kadono, Toshifumi Yamaguchi, Masahiro Goto, Hiroki Nishikawa
Journal: Journal of Clinical Oncology (2024)

334 Background: Nivolumab plus chemotherapy (Nivo-Chemo) is the standard treatment for advanced gastric cancer based on the results of CheckMate 649 trial and ATTRACTION-4 trial. However, real-world data on the efficacy of Nivo-Chemo are limited. This study aimed to assess the efficacy of Nivo-Chemo in the clinical practice setting by comparing it to chemotherapy alone. Methods: We retrospectively reviewed the medical records of patients with advanced gastric cancer who received palliative chemotherapy in our hospital between 2017 and 2023. The inclusion criteria were as follows: age ≥ 20 years; histologically confirmed advanced unresectable or recurrent gastric/gastro-esophageal junction adenocarcinoma; HER2 negative or unknown; and no prior treatment. Patients were divided into two groups based on their first-line treatment: the Nivo-Chemo group and chemotherapy alone (Chemo) group. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were assessed. Results: Of 78 patients, 52 patients were in the Chemo group and 26 patients were in the Nivo-Chemo group. Median age were 69 years (range 30–83) and 67 years (range 39–76) in the Chemo group and Nivo-Chemo group. Eastern Cooperative Oncology Group performance status (ECOG PS) was 0/1/2 in 18/27/7 patients (35%/52%/13%) in the Chemo group and in 17/8/1 patients (65%/31%/4%) in the Nivo-Chemo group. Histological type (Intestinal type/diffuse type) was 19/33 (37%/63%) in the Chemo group and 8/18 (31%/69%) in the Nivo-Chemo group. Combined positive score (CPS) was assessed in 21 patients in the Nivo-Chemo group. The CPS &lt;1/1-5/&gt;5 was in 3/10/8 (12%/38%/31%). In the Chemo group, 28 patients (54%) received anti-PD-1 monotherapy after progression of first-line chemotherapy. The median PFS was 5.7 months in the Chemo group and 6.0 months in the Nivo-Chemo group (HR 0.88, 95% CI 0.50-1.55, p = 0.66). The median OS was 15.0 months in the Chemo group and 18.6 months in the Nivo-Chemo group (HR 0.76, 95% CI 0.37-1.53, p = 0.44). The ORR was 50% in the Chemo group and 54% in the Nivo-Chemo group, while the DCR was 63% and 69%, respectively. Conclusions: In clinical practice, the addition of nivolumab to chemotherapy tended to provide a survival benefit compared to chemotherapy alone.
The impact of Wnt pathway alterations including <i>RNF43</i>, <i>GNAS</i>, <i>CTNNB1</i>, and <i>APC</i> on prognosis and potential therapeutic vulnerability in pancreatic adenocarcinoma (PDAC).
Authors: Naoko Takebe, Edik Matthew Blais, Jasmine Huynh, Dzung Thach, Patricia Miren de Arbeloa, Lynn McCormick Matrisian, Emanuel Petricoin, Michael J. Pishvaian, Vincent Chung, Patrick M Boland, Rona Yaeger, Raymond Couric Wadlow, Andrew Eugene Hendifar, Avinoam Nevler, Timothy Lewis Cannon
Journal: Journal of Clinical Oncology (2024)

698 Background: Several Wnt pathway genes (RNF43, GNAS, CTNNB1, APC) are mutated in PDAC but their clinical implications remain unclear. Both RNF43, a membrane E3 ubiquitin ligase that negatively regulates Wnt via FZD, and GNAS, a mediator of GPCR signaling, are enriched in IPMN-associated PDAC whereas CTNNB1 is a hallmark of solid pseudopapillary neoplasms. Here, we retrospectively analyzed progression-free survival (PFS) and overall survival (OS) in a PDAC cohort to understand potential therapeutic and prognostic differences between tumors with (MUT) or without (WT) Wnt pathway mutations. Methods: We analyzed longitudinal outcomes across 774 patients (pts) with NGS results from Perthera’s Real-World Evidence database who received at least 1 line of therapy in the advanced setting for PDAC. PFS was evaluated from initiation of 1st line for advanced disease until discontinuation due to disease progression. Hazard ratios and p-values were computed via Cox regression when comparing PFS within subsets that received either 1st line FOLFIRINOX (FFX) or 1st line gemcitabine/nab-paclitaxel (GA). Differences in frequencies of genomic alterations outside the Wnt pathway were analyzed by Fisher’s exact test. Results: Within the analysis cohort (N = 774), Wnt pathway alterations were present in 72 (9.3%) of PDAC tumors based on mutations in either RNF43 (4%), GNAS (3%), CTNNB1 (&lt;1%), or APC (2%). Median OS (relative to advanced diagnosis) was significantly longer in the MUT subgroup compared to WT (Table). Median PFS on 1st line GA was significantly longer in MUT pts, and a similar insignificant trend was noted for PFS on 1st line FFX (Table). MSI-high and PIK3CA mutations were enriched for co-occurrence with Wnt pathway alterations whereas common PDAC mutations in KRAS and TP53 were less frequent in MUT pts (Table). Gene-specific trends and potential confounders will be discussed in the context of multivariate OS/PFS analyses. Conclusions: The presence of Wnt pathway alterations identifies a subgroup of advanced PDAC with improved PFS and OS.[Table: see text]