tbuckley/cabot-search huggingface dataset:
Dynamic combined monitoring of SII and PNI in evaluating the prognostic impact on advanced driver gene–negative NSCLC patients receiving immunotherapy.
Authors: Tingting Xu, Haijun Zhang
Journal: Journal of Clinical Oncology (2025)

e20614 Background: In recent years, immune checkpoint inhibitors (ICIs) have become an important treatment option for patients with advanced, driver gene-negative non-small cell lung cancer (NSCLC). This study aims to explore the correlation and predictive value of peripheral blood indicators and clinical characteristics, both before and early during treatment with PD-1 (programmed cell death-1) monoclonal antibody therapy, in relation to the efficacy and prognosis of advanced NSCLC patients. Methods: A retrospective analysis was conducted on patients with advanced, driver gene-negative NSCLC treated with PD-1 inhibitors (either as monotherapy or in combination with chemotherapy) at Zhongda Hospital Southeast University between September 2021 and September 2024. Clinical and laboratory data, including LDH, SII, and PNI, were collected before and after two treatment cycles. Efficacy was assessed using RECIST 1.1, and optimal cutoff values were determined through ROC analysis. Kaplan-Meier and Cox regression analyses were used to identify independent prognostic factors. A prognostic model and nomogram were developed, and their performance was evaluated using C-index, calibration, and ROC AUC. Results: A total of 90 patients were included in the study. ROC analysis determined the optimal cutoff values for pre-treatment and post-treatment (after two cycles) LDH, SII, and PNI. Univariate analysis showed that LDH (T0) ≤ 235.2, LDH (T2) ≤ 227.5, SII (T2) ≤ 631.8, PNI (T2) &gt; 42.6, and the absence of liver metastasis were associated with higher disease control rate (DCR) after four cycles (P &lt; 0.05). LDH (T2) ≤ 227.5, SII (T2) ≤ 631.8, PNI (T2) &gt; 42.6, and the absence of liver metastasis were linked to longer progression-free survival (PFS) (P &lt; 0.05). Pre-treatment LDH ≤ 235.2, post-treatment LDH ≤ 227.5, SII ≤ 631.8, PNI &gt; 42.6, and the absence of liver metastasis were associated with better overall survival (OS) (P &lt; 0.05). Multivariate analysis identified LDH (T2), PNI (T2), and liver metastasis as independent predictors of DCR, PFS, and OS. The multivariate model showed that a greater number of favorable factors was associated with a better prognosis (P &lt; 0.001). Based on these independent factors, nomograms for PFS and OS were developed using R software, with C-indices of 0.786 and 0.792, both &gt; 0.75. Calibration and ROC curve validation indicated good predictive performance for both models. Conclusions: In advanced, driver gene-negative NSCLC patients undergoing ICI treatment, post-treatment (after two cycles) LDH, PNI, and the absence of liver metastasis were associated with treatment efficacy and identified as independent predictive factors. Additionally, post-treatment (after two cycles) SII, PNI, and LDH levels were correlated with patient prognosis and were also independent predictive factors.
Bone marrow polyclonal plasma cells in myeloma post-treatment: Implications on outcome and effect of therapy.
Authors: Miranda Lin, Dragan Jevremovic, Prashant Kapoor, Morie A. Gertz, Angela Dispenzieri, Suzanne R. Hayman, Francis Buadi, David Dingli, Lisa Hwa Christenson, Amie L. Fonder, Miriam A. Hobbs, Yi Lin, Nelson Leung, Taxiarchis Kourelis, Rahma M. Warsame, Mustaqeem Ahmad Siddiqui, Moritz Binder, Nadine Abdallah, S. Vincent Rajkumar, Shaji Kumar
Journal: Journal of Clinical Oncology (2025)

e19531 Background: Effective treatment and elimination of clonal plasma cells (PC) in multiple myeloma (MM) are typically associated with recovery of polyclonal (normal) plasma cells (PPC). Studies suggest that robust PPC recovery is associated with better outcomes. However, it is unclear if this remains valid in the context of monoclonal antibodies, such as Daratumumab, that selectively target plasma cells, and in turn, may adversely impact PPC recovery. Methods: We identified patients with MM who underwent MRD testing using Euroflow method at 6-12 months after treatment initiation. Eight patients had disease progression prior to MRD testing and were excluded from further analysis. PPC was quantitated by the proportion of total events acquired during flow examination. Patients were considered MRD-negative if they had &lt;1 clonal PCs in 10 5 cells, as detected in the marrow. We first examined the impact of initial therapy (Daratumumab vs. non-Daratumumab based regimens) and MRD status on PPC recovery. Subsequently, we analyzed impact of PPC recovery on patient outcomes in terms of progression-free survival (PFS) and overall survival (OS). Results: We identified 572 patients who had MRD testing by flow at a median of 9 months (range 6-12) after treatment initiation. The median age was 63 years, 58% were male. Daratumumab was part of initial therapy in 17% of patients; the most common induction therapies were PI-IMiD triplets (73%), and dara-PI-IMiD quads (15%). In our cohort, 74% of patients were MRD-negative. In our practice, only samples with no monotypic PCs identified on initial low-sensitivity flow proceed to MRD testing, hence, the proportion of MRD-negative patients appears higher in our study than previously reported. Median PPC was 0.02% and was similar between MRD-negative and -positive patients. We found the median PPC was significantly low in patients who received Daratumumab compared to the non-Daratumumab treated cohort (0.011% vs. 0.023%; p&lt;0.01). There was a trend towards lower PFS and OS among the lowest PPC quartile group compared to the upper 3 quartiles, although this was not significant (p=0.07 for PFS and OS, Wilcoxon). This trend was more evident among patients who did not receive Daratumumab. Conclusions: Our study demonstrates negative impact of anti-CD38 therapy with Daratumumab on recovery of PPCs after initial treatment, consistent with the persistent hypogammaglobulinemia seen in clinical practice among these patients. However, unlike the observation with the non-Daratumumab treated cohort, the low proportion of PPCs does not significantly impact patient outcomes among patients who received Daratumumab.
Camrelizumab plus apatinib in patients with advanced or refractory chordoma: A single-arm, open-label, phase 2 trial.
Authors: Cheng Yang, Qi Jia, Chenglong Zhao, Haifeng Wei, Tielong Liu, Xinghai Yang, Jian Jiao, Zhipeng Wu, Jian Zhao, Weiwei Zhou, Xiaomei Ma, Yan Lou, E Zhang, Jingyu Xing, Hao Zhang, Jianru Xiao
Journal: Journal of Clinical Oncology (2025)

11503 Background: The limited efficacy of current treatments for chordoma underscores the need for novel therapeutic options. Immune checkpoint inhibitors (ICI) have changed the landscape of cancer treatment but are rarely investigated for chordomas. Additionally, no established biomarkers reliably predict the efficacy of ICI and targeted therapies in this context. Methods: This investigator-initiated, single-arm, phase 2 trial evaluated the efficacy and safety of camrelizumab (anti-programmed death 1, PD-1) combined with apatinib (a tyrosine kinase inhibitor) in patients with advanced or refractory chordoma. Eligible patients received camrelizumab (200 mg intravenously every 2 weeks) and apatinib (250/500 mg orally daily) in 28-day cycles. The primary endpoint was objective response rate (ORR) assessed per RECIST 1.1 and Choi criteria. Secondary endpoints were median progression-free survival (PFS), overall survival, disease control rate (DCR) and safety. Next-generation sequencing (NGS) and fluorescence in situ hybridization (FISH) were used to explore predictive biomarkers. The trial is registered on Chictr.org.cn (ChiCTR2100042938). Results: Between September 2021, and October 2024, 38 patients were screened, and 33 were enrolled for efficacy and safety analyses. The median treatment duration was 7 months (IQR 4-14), with a median radiologic evaluation time of 10 months (IQR 9-13) and median follow-up of 15 months (IQR 9-22). At data cutoff, 15 (45.5%) patients remained on treatment. Per RECIST 1.1, seven patients (21.2%, [95% CI, 9.0-38.9]) achieved partial response (PR), with a 6-month DCR of 85.2% (23/27). The median PFS was 18.1 months (95% CI, 11.0-28.5). According to Choi criteria, 16 patients (48.5%, [95% CI, 30.8-66.5]) achieved PR, with a 6-month DCR of 77.7% (21/27) and a median PFS of 15.3 months (95% CI, 10.6-NE). Two patients died of tumor progression, and two others with cervical recurrent chordoma died from postoperative complications. NGS analyses revealed copy number deletion (CND) of CDKN2A in 30% (6/20) of cases. Post hoc FISH analysis of 25 specimens identified homozygous deletion (HD) of CDKN2A in 40.0% (10/25), which correlated with poorer outcomes. Adverse events (AEs) occurred in 93.9% (31/33) of patients, with grade 3/4 AEs in 48.5%. Treatment-related AEs led to apatinib dose interruptions in 39.4% and camrelizumab interruptions in 21.2%. Conclusions: The combination of camrelizumab and apatinib demonstrated promising efficacy and manageable toxicity in chordoma treatment. Furthermore, CDKN2A alterations (CND or HD) were associated with poorer outcomes, providing a potential biomarker for therapeutic stratification. Clinical trial information: ChiCTR2100042938 .
Early assessment of response to chemotherapy via ctDNA in soft tissue sarcoma.
Authors: Maggie Yuxi Zhou, Minggui Pan, Nam Bui, Kristen N. Ganjoo
Journal: Journal of Clinical Oncology (2025)

11531 Background: Chemotherapy remains the cornerstone for treatment of soft tissue sarcomas (STS). Biomarkers are needed to enhance timely assessment of chemotherapy efficacy to limit toxicity and guide patient management including estimating prognosis and duration of chemotherapy. Methods: This retrospective study includes patients with STS who received chemotherapy in the neoadjuvant or unresectable/metastatic setting at Stanford Sarcoma Center between May 2021 and January 2025. ctDNA was tested with Natera’s CLIA lab using a personalized, tumor-informed ctDNA assay (Signatera, bespoke mPCR, NGS assay). Longitudinal changes in peripheral blood ctDNA were correlated with radiographic response and survival. ctDNA response was defined as &gt; 50% decrease in MTM/mL from baseline, with a second confirmatory measurement. Radiographic response was defined as stable disease or partial response on first re-staging assessment after starting therapy. Overall survival (OS) was defined as time from initiation of chemotherapy to death or last clinical follow up. Progression-free survival (PFS) was defined as time from initiation of chemotherapy to radiographic disease progression, death, or last clinical follow up. Results: Twenty-six patients (median age at diagnosis = 63 years [range 26 – 78]) were included. Histological subtypes consisted of leiomyosarcoma (uterine [n = 10], extrauterine [n = 4]), malignant peripheral nerve sheath tumor (n = 2), undifferentiated pleomorphic sarcoma (n = 2), angiosarcoma (n = 2), and other (Ewing’s sarcoma, malignant phyllodes tumor, perivascular epithelioid cell tumor, low grade myoepithelial carcinoma, high grade uterine sarcoma not otherwise specified, and small round blue cell neoplasm with EWSR1 rearrangement, each n = 1). Chemotherapy consisted of doxorubicin-containing regimens (n = 9), gemcitabine/docetaxel (n = 9), temozolomide-containing regimens (n = 5), and other (cyclophosphamide/topotecan, paclitaxel, and trabectedin, each n = 1). Median follow-up time after initiation of chemotherapy was 12.9 months. 16 of 26 patients had radiographic response. Substantial agreement was observed between ctDNA response and radiographic response (Cohen’s kappa coefficient 0.752). Median OS was longer for ctDNA responders (n = 17) than non-responders (n = 9), at 43.8 months vs 20.6 months (p = 0.03). Median PFS was longer for ctDNA responders than non-responders, at 11.4 months vs 2.0 months (p &lt; 0.001). In the metastatic cohort (n = 22), time on chemotherapy regimen was longer for ctDNA responders than non-responders, median 5.0 vs 2.6 months, p = 0.016 by Wilcoxon rank sum test. Conclusions: Early decline in ctDNA after initiation of chemotherapy correlates with radiographic response and survival in STS. Research is ongoing to evaluate these findings in a prospective study.
Second-line treatment patterns and outcomes of advanced gastrointestinal stromal tumor: A real-world study.
Authors: Xinhua Zhang, Anni Chen, Jun Zhang, Hao Sun, Miao Liu, Xingyu Feng, Xiaojun Wu, Huaiming Wang, Yuan Yin, Xiaoting Wu, Zhi Ding, Yongdong Jin, Minghui Pang, Zhuofei Li, Lie Wang, Ling Fan, Yong Liu, Xu Che, Mengqiao Wang, Yanzhe Xia
Journal: Journal of Clinical Oncology (2025)

11526 Background: Ripretinib has emerged as a promising second-line therapy for patients with unresectable or metastatic gastrointestinal stromal tumors (GISTs), demonstrating comparable efficacy to sunitinib and a superior safety profile. However, the optimal second-line therapy tailored to individual patient characteristics remains underexplored. This prospective, multicenter, observational study (NCT05440357) aims to evaluate real-world patterns and outcomes for GISTs patients. Methods: The choice of second-line regimen was determined by the investigators. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety, objective response rate (ORR), and overall survival (OS). Results: From October 2022, 99 patients were enrolled (ripretinib, n = 49; sunitinib, n = 47; regorafenib, n = 3), with a median follow-up of 8.0 months. Among ripretinib-treated patients, 69% (34/49) had primary KIT exon 11 mutations, while 47% (22/47) of sunitinib-treated patients had primary KIT exon 9 mutations. The objective response rates were 20% (10/49) for ripretinib, 9% (4/47) for sunitinib, and 0% for regorafenib. Median PFS (mPFS) for ripretinib, sunitinib and regorafenib was 11.4, 12.4 and 2.8 months, respectively (p = 0.296). Ripretinib demonstrated better mPFS in patients with primary KIT exon 11 mutations compared to sunitinib group (11.4 vs 7.0 months, p = 0.048). In patients with KIT exon 9 mutations, mPFS was 15.0 months for sunitinib. Ripretinib was associated with fewer grade 3/4 treatment-emergent adverse events (TEAEs) compared to sunitinib (10%vs 26%, p = 0.044). OS data are currently immature. Additionally, 27% (13/49) of patients treated with ripretinib and 17% (8/47) with sunitinib underwent surgery. Among patients who underwent surgery following ripretinib treatment, 84.6% (11/13) achieved R0/R1 resection. 100% (8/8) patients achieved R0/R1 resection in sunitinib group. Median postoperative PFS for ripretinib and sunitinib was 15.5 months and 10.2 months, respectively (p = 0.350). Conclusions: This study is the first prospective, multicenter, real-world study to compare different second-line targeted drugs for advanced GISTs. Our preliminary results suggest that ripretinib may offer superior clinical benefits for patients with primary KIT exon 11 mutations after failure of imatinib first line treatment. Its favorable safety profile and improved tumor response rate facilitated a higher rate of surgical intervention compared to sunitinib. The benefit of surgery remains to be observed. Clinical trial information: NCT05440357 .
The impacts on prognosis of the relationship between decline in renal function associated with pemetrexed and the ratio of pemetrexed administration.
Authors: Yuta Yamanaka, Kenta Murotani, Hiroshige Yoshioka, Kazuki Fujii, Yutaro Nagata, Yukiko Okuno, Keisuke Kamisako, Yuta Okazaki, Kentaro Nakanishi, Kiyori Yoshida, Ikoma Tatsuki, Yuki Takeyasu, Utae Katsushima, Takayasu Kurata
Journal: Journal of Clinical Oncology (2025)

e20623 Background: The KEYNOTE 189 regimen of pembrolizumab + pemetrexed + cisplatin/carboplatin is currently being used as first-line chemotherapy for metastatic non-squamous non-small cell lung cancer (NSCLC). However, there are many patients who cannot continue chemotherapy due to decreased renal function caused by pemetrexed. Methods: We extracted data from the electronic medical records of 106 patients diagnosed with metastatic non-squamous non-small cell lung cancer who received the KEYNOTE 189 regimen at our facility between December 2018 and March 2024, and conducted an analysis. With regard to renal function, creatinine clearance was calculated at three points in time: before treatment, at the start of maintenance therapy, and at the time of disease progression, and the trend in prognosis was examined using the rate of change (ΔCcr). With regard to the dose of pemetrexed, the trend in prognosis was examined using the total amount of pemetrexed administered/the maximum scheduled dose of pemetrexed (the ratio of pemetrexed administered). Results: In our institution, the mPFS and mOS in the ITT population were 8.3 months (95% CI, 6.4-9.5) and 20.0 months (95% CI, 14.4-26.94), and there was no significant difference from the KEYNOTE189 study. ΔCcr from the start of treatment to the start of maintenance therapy tended to have the most impact on prognosis, and an increase in ΔCcr was associated with a poorer prognosis, with a maximum HR of 2.53 (95% CI, 1.31-4.86) when ΔCcr was 28.72. In addition, there was a trend towards worse prognosis as the pemetrexed administration ratio increased, with a maximum HR of 4.75 (95% CI, 2.45-9.22) at a pemetrexed administration ratio of 0.307. When the groups were divided into four using these two cutoff values, there was a statistically significant difference in OS in the group with a low-low ΔCcr- ratio of pemetrexed administered. Conclusions: Our study suggests that suppressing the decline in renal function during the induction chemotherapy period and then not administering pemetrexed may lead to the best survival outcomes. There is therefore a need for comparative studies to determine the necessity of pemetrexed maintenance therapy in the KEYNOTE189 regimen.
ETCTN 10563: A phase I study of peposertib and liposomal doxorubicin for advanced or metastatic leiomyosarcoma and other sarcomas.
Authors: Candace L. Haddox, Karla V. Ballman, Elise F. Nassif Haddad, Scott Michael Schuetze, Melissa Amber Burgess, Alice P. Chen, Ludimila Cavalcante, Emily E. Jonczak, Brian Andrew Van Tine, Steven Gore, Jonathan Fletcher, Suzanne George
Journal: Journal of Clinical Oncology (2025)

TPS11585 Background: Soft tissue sarcomas (STS) with genomic complexity are often aggressive but may be sensitive to further genotoxic stress. Leiomyosarcoma (LMS), a common STS, frequently harbors genomic complexity and DNA damage response (DDR) dysregulation. Preclinical data showed hyper-dependency on DNA-PK-mediated non-homologous end joining (NHEJ) DDR, and low-dose liposomal doxorubicin (LD-LPD) synergized with the DNA-PK inhibitor peposertib to inhibit tumor growth in LMS models. We hypothesize that a low, sensitizing dose of LPD enhances DNA damage and safely synergizes with peposertib in LMS and other genomically complex STS. Methods: This phase 1, open label, multicenter dose escalation and dose expansion study (NCT05711615) evaluates LD-LPD given intravenously (IV) on day 1 of 28-day cycles with peposertib given orally (PO) twice daily (BID) continuously (Table). Up to 18 patients (pts) over 18 years-old with advanced or unresectable LMS, undifferentiated pleomorphic sarcoma, myxofibrosarcoma, dedifferentiated liposarcoma, and synovial sarcoma, ECOG performance status ≤2, who received ≥1 prior line of systemic therapy (including anthracycline ≤300 mg/m 2 ) are eligible for dose escalation. Dose expansion will include 12 pts with LMS. The primary objective is to determine the recommended phase 2 dose of LPD+peposertib based on the dose limiting toxicity rate. The Bayesian Optimal Interval (BOIN) design will inform dose escalation decisions. Secondary endpoints for the expansion cohort include adverse event rate, progression-free survival, and objective response rate per RECIST v1.1. Potential predictive biomarkers and changes in DDR biomarkers will be evaluated on biopsies during screening and at cycle 1 day 7. Circulating tumor DNA (ctDNA) collected at baseline (dose escalation and dose expansion), on treatment and at progression (dose expansion) will be correlated with disease activity and response. This trial activated on 8-May-2023 through the Experimental Therapeutics Clinical Trials Network (ETCTN) and is enrolling at select sites in the United States. Dose escalation is ongoing as of January 2025. Clinical trial information: NCT05711615 . Planned dose levels for dose escalation. Dose Escalation Schedule Dose Level Dose Liposomal doxorubicin Peposertib (tablet) -1 10 mg/m 2 IV 50 mg PO BID 0* 10 mg/m 2 IV 100 mg PO BID +1 10 mg/m 2 IV 150 mg PO BID +2 10 mg/m 2 IV 200 mg PO BID +3 15 mg/m 2 IV 200 mg PO BID +4 20 mg/m 2 IV 200 mg PO BID *Starting dose.
Impact of tumor burden on outcomes after immune versus conventional therapies.
Authors: Prashanth Gowda, David Hsieh
Journal: Journal of Clinical Oncology (2025)

e20621 Background: Tumor burden has been previously suggested to be an important determinant of immunotherapy efficacy due to tumor bulk impeding lymphocyte infiltration, and a greater concentration of immunosuppressive tumor-derived factors. However, a higher tumor burden may also lead to a greater neoantigen load resulting in a greater potential for eliciting immune responses with immune checkpoint inhibitors. Whether tumor burden is a specific predictor of immunotherapy outcomes remains ambiguous. Methods: To determine whether tumor burden is associated with immunotherapy outcomes, we conducted an analysis of 2980 patients with individual-level data from eight clinical trials across four different cancer types: NSCLC, RCC, HCC, and bladder cancer. Kaplan-Meier survival analysis was used to estimate and compare survival probabilities across different treatment groups and tumor burden. Progression-free survival (PFS) and overall survival (OS) were selected as the primary survival endpoints. Patients were stratified into subgroups based on treatment modality (immune checkpoint inhibitor [ICI] therapy vs. chemotherapy) and tumor burden (low vs. high), with tumor burden defined using the sum of the longest diameters (SLD). Patients were ranked by SLD, and those in the lower half of the SLD distribution were categorized as having low tumor burden, while those in the upper half were categorized as having high tumor burden. Results: In patients with NSCLC, RCC, and bladder cancer, PFS was decreased in patients with higher tumor burden in ICI treated patients and conventional therapy treated patients. In HCC, there was no statistically significant difference in PFS between high and low tumor burden patients. Across all cancer types, OS was uniformly inferior in high tumor burden patients treated with ICI and with chemotherapy. Objective tumor response rates including partial and complete responses were decreased in patients with high tumor burden treated with either immunotherapy or conventional therapy. Conclusions: These results demonstrate that tumor burden is generally associated with worse outcomes regardless of treatment context, suggesting that tumor burden is a prognostic factor of advanced stage cancers undergoing systemic treatment rather than a predictive marker of immunotherapy. Tumor burden may thus be an important stratification factor for trials testing systemic therapies regardless of their mechanism of action.