tbuckley/cabot-search huggingface dataset:
Next-generation sequencing (NGS) completion and timeliness using reflex testing protocol for patients with stage II-III non-squamous non-small cell lung cancer (NS-NSCLC).
Authors: Shipra Maheshwari, Gordon Smilnak, Rishika Singh, Eli Williams, Edward B Stelow, Subodh Pandey, Linda Martin, James Mitchell Larner, Richard Delmar Hall, Ryan D. Gentzler
Journal: Journal of Clinical Oncology (2024)

8060 Background: Genomic testing is important for early-stage NSCLC due to benefits of adjuvant EGFR and ALK targeted therapies and implications for neoadjuvant immunotherapy decisions. The purpose of this study is to evaluate the completion rates and timeliness of NGS prior to treatment initiation for patients with stage II-III NS-NSCLC, with reflex NGS testing protocols in place. Methods: Patients with stage II-III NS-NSCLC diagnosed between 2015 and 2022 at UVA Cancer Center were identified retrospectively. A reflex tissue-based NGS testing protocol was initiated at UVA in early 2015 using in-house TruSight Tumor and later PGDx platforms. Targeted pyrosequencing was performed in cases of NGS failures. The primary outcomes of the study were to evaluate the NGS completion rate and median time from biopsy to results and to any first line treatment (1L), including surgery, radiation, or systemic therapy. Actionable mutation incidence, proportion of patients with test results prior to treatment, and overall survival (OS) were all assessed. Statistical analysis included both descriptive statistics and Kaplan-Meier methodology for overall survival (OS). Results: 171 patients met eligibility, 92 (54%) female, 80 (47%) stage II and 91 (53%) stage III. 159 (93%) had known 1L start dates and 99 (58%) received systemic therapy with known dates. Testing completion rates and time to results are shown in the table. Actionable mutations identified included: KRAS 39% (G12C 15%), EGFR 7%, BRAF 4%, MET 2%, RET 1%, and NTRK 1%. There was no difference in NGS success rates between patients with stage II and III diseases, X 2 (1, N = 171) = 2.667, p = 0.102. Median OS was 64.1 months in those with complete NGS testing and 53.4 months in those without complete NGS (p=0.222). Conclusions: Reflexive, in-house NGS resulted in a shorter median time from biopsy to results (17 days) and higher completion rate (NGS, 77%; at least limited testing, 92%) compared to historical controls. The majority of patients had NGS results available to inform systemic therapy decisions (69%). While OS was numerically higher for patients with complete NGS, this was not statistically significant. Reflex NGS testing protocols increase the likelihood of obtaining timely results in the new era of adjuvant tyrosine kinase inhibitors and neoadjuvant chemotherapy and immunotherapy. [Table: see text]
Four-year outcomes and circulating tumor DNA (ctDNA) analysis of pembrolizumab (pembro) plus concurrent chemoradiation therapy (cCRT) in unresectable, locally advanced, stage III non–small-cell lung cancer (NSCLC): From KEYNOTE-799.
Authors: Martin Reck, Ki Hyeong Lee, Nikolaj Frost, Valeriy Vladimirovich Breder, Dariusz M. Kowalski, Evgeny Levchenko, Noemi Reguart, Alex Martinez-Marti, Baerin Houghton, Jean-Baptiste Paoli, Sufiia Safina, Hong Liu, Vladimir Novinskiy, E.J. Dettman, Julie Kobie, Salma K. Jabbour
Journal: Journal of Clinical Oncology (2024)

8057 Background: The nonrandomized phase 2 KEYNOTE-799 study (NCT03631784) of pembro + cCRT in previously untreated unresectable, locally advanced, stage III NSCLC demonstrated an ORR of 70.5% in cohort A (squamous and nonsquamous) and 70.6% in cohort B (nonsquamous only) after median follow-up of 18.5 mo and 13.7 mo, respectively. We present outcomes with ⁓4 y of follow-up and analysis of ctDNA. Methods: Eligible patients (pts) were aged ≥18 y with unresectable confirmed stage IIIA–C NSCLC (per AJCC v8), measurable disease per RECIST v1.1, and ECOG PS 0 or 1. Pts in cohort A (squamous and nonsquamous) received carboplatin + paclitaxel and pembro 200 mg for one 3-wk cycle, followed by carboplatin + paclitaxel QW for 6 wks + 2 cycles of pembro 200 mg Q3W + standard thoracic radiotherapy (TRT). Pts in cohort B (nonsquamous only) received 3 cycles of cisplatin, pemetrexed, and pembro 200 mg Q3W + standard TRT in cycles 2 and 3. All pts received 14 additional cycles of pembro. Primary endpoints were ORR per RECIST v1.1 by BICR and incidence of grade ≥3 pneumonitis (per NCI CTCAE v4.0). As an exploratory endpoint, tumor ctDNA was assessed in available plasma samples collected at baseline and cycle 7 using the Signatera ctDNA assay. Results: Of 214 pts enrolled, including 112 in cohort A and 102 in cohort B. Median (range) time from first dose to database cutoff (Oct 16, 2023) was 54.1 (49.2–59.4) and 49.3 (38.4–59.1) mo, respectively. ORR was 71.4% in cohort A and 74.5% in cohort B (Table). Grade ≥3 pneumonitis (primary endpoint) occurred in 9 pts (8.0%) in cohort A and 7 (6.9%) in cohort B. Grade 3–5 treatment-related AEs occurred in 73 pts (65.2%) in cohort A and 52 (51.0%) in cohort B. Of ~136 samples sent for sequencing, 73 pts (~53.7%) had samples evaluable for ctDNA at baseline. ORR was 68.7% in pts with ctDNA detectable (n = 67) vs 50.0% in pts with ctDNA non-detectable samples (n = 6) at baseline. Among 46 pts with ctDNA detectable at baseline and evaluated at cycle 7, 32 (69.6%) had cleared ctDNA at cycle 7; these pts had better trends in PFS and OS vs pts who had not cleared ctDNA at cycle 7 (n = 14). Conclusions: With ~4 y of follow-up, pembro + cCRT continues to demonstrate durable antitumor activity and manageable safety in previously untreated unresectable, locally advanced stage III NSCLC. ctDNA was evaluable in ~half of the samples assessed; most pts with detectable ctDNA at baseline had cleared ctDNA at cycle 7. Clinical trial information: NCT03631784 . [Table: see text]
Treatment outcomes in locally advanced, unresectable NSCLC treated with concurrent chemoradiation and PD-L1 consolidation: Real-world data from a NCI comprehensive cancer center with a racially diverse, high poverty catchment area.
Authors: Matthew M. Mirsky, Ho Jun Lee, Seunghee P Margevicius, Alex Carsel, Katherine Myers, Kevin Zablonski, Jeffrey Zhong, Pingfu Fu, Qian Wang, Afshin Dowlati, Debora S. Bruno, Melinda Laine Hsu
Journal: Journal of Clinical Oncology (2024)

8067 Background: The PACIFIC trial established concurrent chemoradiotherapy (CCRT) followed by consolidation durvalumab as standard of care for unresectable stage III non-small cell lung cancer (NSCLC). This study showed a progression free survival (PFS) of 16.9 mo and an overall survival (OS) of 47.5 mo. There is a paucity of real world data with PACIFIC, especially in diverse patient populations. We present real world outcomes of the PACIFIC regimen in a NCI-designated comprehensive cancer center (CCC) with a racially diverse, high poverty catchment area. Methods: Retrospective chart review identified patients treated with durvalumab for NSCLC after CCRT per PACIFIC. Demographic data included sex, race, age, stage, address, smoking status, immunotherapy adverse events (irAE). Poverty index was assessed using the SAIPE tool by percent of children in poverty at the school district level based off 2021 census and stratified to above and below 15.1%. Annual air particulate matter (PM) 2.5 was obtained at the zip code level from the Socioeconomic Data and Applications Center. PFS was from date of first dose durvalumab; OS was from date of NSCLC diagnosis to death or last follow up. Results: 203 patients with unresectable NSCLC were included. Of these, 18.2% were of Black race compared to 2.0% in the PACIFIC trial. 42.4% of patients lived in high poverty areas, 44.3% were current smokers. Patients had a median annual PM 2.5 exposure of 7.9 ug/m 3 . 42.7% had PD-L1 expression &gt;50%. The irAE rate was 27.6% (Table 1). Overall median PFS was 23 mo (95% CI 16.1-31.9) and 28.2 mo (95% CI 11.1-50.7) for patients of Black race. Overall median OS was 52.4 mo (95% CI 31.2-NR) and 52.4 mo (95% CI 18.2-NR) for Black patients. Conclusions: In this diverse cohort treated with the PACIFIC regimen at a NCI CCC, favorable real world PFS (23.0 vs. 16.9 mo), and OS (52.4 vs. 47.5 mo) were demonstrated. This cohort is more representative of the US patient population than that of a stringent clinical trial population with at least comparable results. This unexpected result may arise from institutional practices leading to equitable access to care and other biological characteristics of the population. Clinical trial enrollment representative of the broader population remains paramount for equitable care delivery. [Table: see text]
CA-62: A new biomarker for the detection of early-stage renal cell carcinoma.
Authors: Janneta Tcherkassova, Sergei Tsurkan, Anna Prostyakova, Evgueni Klinski, Marina Sekacheva, Alexander Boroda, Ricardo Moro
Journal: Journal of Clinical Oncology (2024)

4526 Background: The American Cancer Society classifies Renal Cell Carcinoma (RCC) to be among the ten most common cancers. However, in spite of this need, effective biomarkers for early-stage detection of RCC are not yet available. The purpose of this study was to assess the diagnostic characteristics of a carcinoma-specific transmembrane N-glycoprotein biomarker, CA-62, for the detection of early-stage kidney cancer. Blinded serum samples from 204 patients were included in the clinical study, of which 68 had TNM-classified stages IA, IB, IIA or IIB renal cell carcinomas, while 136 were drawn from healthy volunteers. Methods: Quantitative measurement of serum CA-62 levels was performed using a chemiluminescent immunoassay ("JVS Diagnostics" LLC). Statistical analysis (MedCalc; version 19.7.4, MedCalc Software Ltd, Belgium, EU) was used to assess the diagnostic characteristics of the CA-62 biomarker for detection of RCC, including sensitivity and specificity, and test accuracy. Results: Significantly higher median concentrations of CA-62 were found in sera of RCC patients compared to those found in healthy controls as follows; stage I A, B (8,935 U/mL), stage II A (6,291 U/mL), stage II B (8,808 U/mL), and healthy controls (2,815 U/mL). It was expected that serum CA-62 levels would be elevated at these early stages of RCC (Stages I-IIB), demonstrating significant overexpression of this epithelial carcinoma marker during the initial stages of cancerogenesis. The results of the study are presented in the table. Area under the ROC curve (AUC) for RCC patients vs. healthy controls was 0.98 with a 95% CI (0.950-0.994), z-statistics (67.3), and a significance of p&lt;0.0001. Conclusions: CA-62 demonstrated a 94.3% sensitivity for RCC at 96% specificity during the early stages of kidney cancer. Given that CA-62 is not specific for kidney cancer, it is reasonable to suggest that use of a combination of CA-62 with some other biomarkers that may lack the sensitivity of CA-62 but are often elevated in renal cell carcinoma patients, such as tumor-infiltrating lymphocytes and/or possibly some inflammation biomarkers. In particular, the combination of transmembrane glycoproteins CA-62 and CD105, combined with biomarkers such as Endothelial Vascular Growth Factor (EVGF) and/or a growth factor derived from platelets (PDGF) could be successfully used for kidney cancer screening in order to achieve both high sensitivity and specificity for RCC detection.[Table: see text]
A phase II trial of alternating mXELOX/mXELIRI plus bevacizumab (BEV) as first-line treatment for metastatic colorectal cancer (mCRC).
Authors: Sheng Li, Liangjun Zhu, Xiaoyou Li, Jiayuan Huang, Hanfeng Xu
Journal: Journal of Clinical Oncology (2024)

3574 Background: First-line fluoropyrimidine (FL), oxaliplatin (OX), irinotecan (IRI) plus BEV had better efficacy but worse safety vs FL, IRI plus BEV for mCRC. Preliminary data showed promising anti-tumor activity and acceptable toxicity of alternating FL plus OX and FL plus IRI. This study aimed to assess the alternating schedule of modified capecitabine (XEL), OX (i.e., mXELOX) plus BEV and modified XEL, IRI (i.e., mXELIRI) plus BEV for mCRC. Methods: This single-arm phase II trial was conducted in China. Patients aged 18–75 years, with histologically confirmed unresectable mCRC, ≥one measurable lesion via RECIST v1.1, ECOG PS of 0 to 2, and life expectancy of ≥3 months were eligible. Prior systemic therapies were not allowed except adjuvant chemotherapy. Induction treatment consisted of XEL 1000 mg/m 2 bid D2–8 and D16–22, OX 85 mg/m 2 D1, IRI 150 mg/m 2 D15, and BEV 5 mg/kg D1 and 15 for 28-day cycles (up to six cycles). XEL 1000 mg/m 2 bid D2–15 and BEV 7.5 mg/kg D1 for 21-day cycles were used as maintenance treatment. The primary endpoint was progression-free survival (PFS). Results: Between Apr 2020 and May 2023, 52 patients were included. As of Dec 30, 2023, median follow-up was 25.0 months. Mean age was 58.5±9.1 years old. 28 (54%) were male. 45 (87%) patients had either right-sided diseases, RAS or BRAF mutations. Median PFS was 11.0 months (95% CI 9.0–12.4). Subgroup analyses showed prior treatments, tumor locations and metastases, and BRAF mutations did not affect efficacy. RAS wild-type patients had longer PFS vs mutant patients (median 12.3 months vs 9.8 months; P=0.024). Objective response rate and disease control rate were 73% (59%–84%) and 94% (84%–99%), respectively. Overall survival (OS) reached 28.1 months (18.4–34.0). Efficacy data were detailed in the Table. Grade 3–4 treatment-related adverse events (TRAE) occurred in 17 (33%) of 52 patients. No treatment-related death was reported. The most common grade 3–4 TRAE were hypertension (13 [25%]), neutrophil count decreased (three [6%]), and hand-foot syndrome (two [4%]). Additionally, grade 3–4 TRAE of diarrhoea occurred in one [2%] patient and no grade 3–4 peripheral neuropathy was reported. Conclusions: Alternating mXELOX/mXELIRI plus BEV demonstrated promising anti-tumor activity against mCRC, with acceptable tolerability and no new safety signal. Further studies were warranted to confirm the efficacy of the regimen. Clinical trial information: NCT04324476 . [Table: see text]
Extent of lymphadenectomy for surgical management of right-sided colon cancer: Multicenter, open label, randomized, controlled trial.
Authors: Yi Xiao, Junyang Lu, Xiangqian Su, Minhua Zheng, Yueming Sun, Xiaohui Du, Pan Chi, Ziqiang Wang, Ming Zhong, Aiwen WU, Anlong Zhu, Fei Li, Jianmin Xu, Liang Kang, Jian Suo, Haijun Deng, Yingjiang Ye, Ke-Feng Ding, Zhongtao Zhang
Journal: Journal of Clinical Oncology (2024)

3575 Background: Complete mesocolic excision (CME) is being increasingly used for the treatment of right-sided colon cancer although there is still no strong evidence that CME provides better long-term oncological outcomes than D2 dissection. The controversy is mainly regarding the survival benefit from extended lymph node dissection emphasized by CME. Methods: This randomized, controlled, unblinded, phase 3, superiority trial involved 17 hospitals in China. Totally 1,072 patients diagnosed with stage T2-T4aNanyM0 or TanyN+M0 right-sided colon cancer were enrolled from January 11, 2016, through December 26, 2019. Participants were randomly assigned (1:1 ratio) to undergo either CME (n=536) or D2 dissection (n=536) during laparoscopic right colectomy. The primary outcome was the 3-year disease-free survival (DFS), and the main secondary outcome was the 3-year overall survival (OS). Results: Among 1072 patients, 77 were excluded after randomization. The remaining 995 patients (median age 61years, 59% male) were included in the primary analysis (CME [n=495] vs. D2 dissection [n=500]). The 3-year primary outcome assessment was completed for 97% patients. No significant differences were found between the groups in 3-year DFS (86.1% in CME group vs. 81.9% in D2 group; HR = 0.74; 95% confidence interval [CI]: 0.54-1.02; P = 0.06) or in 3-year OS (94.7% in CME group vs. 92.6% in D2 group; HR = 0.70; 95% CI: 0.43-1.16; P = 0.17). Conclusions: For primary surgical excision of right-sided colon cancer, complete mesocolic excision did not improve disease free survival, compared to standard D2 lymph node dissection. Standard D2 dissection should be the routine procedure for these patients. CME should only be considered in patients with obvious mesocolic lymph node involvement. Trial Registration: ClinicalTrials.gov Identifier: NCT02619942. Clinical trial information: NCT02619942 .
Iparomlimab (QL1604) in patients (pts) with unresectable/metastatic deficient mismatch repair (dMMR)/microsatellite instability high (MSI-H) solid tumors: A single-arm, multicenter, pivotal, phase II study.
Authors: Weijian Guo, Feng Bi, Jian Dong, Chuan Jin, Zuoxing Niu, Yusheng Wang, Meili Sun, Teng Wang, Dajun Yu, Yifu He, Ruixing Zhang, Xianli Yin, Wenlei Feng, Meijiang Zhang, Baihui Zhang, Lingyan Li, Xiaoyan Kang
Journal: Journal of Clinical Oncology (2024)

3578 Background: Iparomlimab, a novel anti-PD-1 antibody, demonstrated robust anti-tumor activity and well tolerated safety in pts with unresectable/metastatic dMMR/MSI-H solid tumors. At median follow-up of 17 mo, iparomlimab treatment demonstrated durable clinical benefit. Methods: This phase II study (NCT04326829) enrolled pts pathologically diagnosed as dMMR/MSI-H unresectable/metastatic solid tumors. Pts received iparomlimab (200 mg, iv, Q3W; 3 mg/kg for pts with body weight &lt;40 kg). The primary endpoint was confirmed objective response rate (ORR) assessed by independent radiological review committee (IRRC) per RECIST 1.1. Eligible pts, who were enrolled and received at least 1 cycle of treatment, were included in the intention to treat (ITT) set. Among them, relapsed/refractory pts were included in the full analysis set (FAS) as primary efficacy analysis population. The FAS included pts with advanced colorectal cancer (CRC) failed from fluoropyrimidine, oxaliplatin, and irinotecan, pts with gastric cancer failed from at least two lines of standard of care, and other solid tumors failed from at least one prior treatment. Results: From Jun 19, 2020 to Jan 12, 2023, 120 pts were enrolled in ITT, with 60 pts in FAS. 117 (97.5%) pts were featured with stage IV disease. The median prior therapy lines were 2.0 in both ITT and FAS, respectively. CRC was diagnosed in 80 (66.7%) pts in ITT and 38 (63.3%) pts in FAS. As of Jan 20, 2024, the ORR were 58/120 (48.3%; 95% CI: 39.1%–57.6%) with 12 (10.0%) complete response (CR) and 46 (38.3%) partial response (PR) in ITT, and 30/60 (50.0%, 36.8%–63.2%) with 3 (5.0%) CR and 27 (45.0%) PR in FAS. In CRC pts, the ORR per IRRC were 37/80 (46.3%) and 22/38 (57.9%) in ITT and FAS, respectively. (Efficacy shown in Table) TRAEs of any grade occurred in 95 (79.2%) pts. The most frequent TRAE of any grade and grade ≥3 TRAE were both anemia, with incidence of 26.7% and 5.0%, respectively. irAEs of any grade were reported in 39/120 (32.5%) pts, with the most common occurring irAEs of hpothyroidism (12/120, 10.0%). TRSAEs occurred in 13/120 (10.8%) patients. No iparomlimab-related death occurred. Conclusions: At 17-mo follow-up, iparomlimab showed encouraging efficacy with durable response and tolerable safety in patients with unresectable/metastatic dMMR/MSI-H solid tumors in ITT and FAS. Clinical trial information: NCT04326829 . [Table: see text]
Sintilimab plus axitinib for advanced fumarate hydratase-deficient renal cell carcinoma: A multi-center, open-label, single-arm, phase II study (SAFH).
Authors: Hao Zeng, Xingming Zhang, Jiayu Liang, Junjie Zhao, Haoyang Liu, Yaowen Zhang, Yuntian Chen, Guangxi Sun, Xinan Sheng, Yongquan Wang, Xiaodong Liu, Rui Huang, Qiang Wei, Xiang Li, Jiyan Liu, Pengfei Shen, Pengfei Shen, Ni Chen, Jin Yao, Zhenhua Liu
Journal: Journal of Clinical Oncology (2024)

4523 Background: Fumarate hydratase-deficient renal cell carcinoma (FH-dRCC) is a rare and highly invasive subtype of renal cell carcinoma. Previous studies have shown that immune checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) can be considered for first-line systemic treatment of FH-dRCC. We aimed to provide high-quality prospective clinical trial evidence regarding the efficacy and safety of Sintilimab plus Axitinib in FH-dRCC. Methods: This study was an investigator-initiated, open-label, single-arm, multiple institutional, phase II trial in patients (pts) aged 18 years or older with treatment naive, advanced FH-dRCC. Patients received Sintilimab (intravenous injection, every 3 week) in combination with Axitinib (5mg, orally taken per day) as first-line treatment until disease progression or intolerant to treatment. The primary endpoint was objective response rate (ORR; RECIST v1.1) and progression-free survival (PFS). This study is registered with ClinicalTrials.gov, NCT04387500. Results: From June 2021 to August 2023, 52 patients were screened, and 41 patients were enrolled. The median follow up was 16.0 months. Thirty-eight patients were available for efficacy assessment. Confirmed complete response rate was 10.5% (4/38), ORR was 60.5% (23/38). Disease-controlled rate (DCR) was 86.8%. The median PFS was 19.83 months (95% CI: 7.68-31.99). All grade and ≥3 treatment-emergent adverse events occurred in 87.8% (36/41) and 22.0% (9/41), respectively. Details about FH mutation status were available in 40 patients, and different FH mutation patterns were found to be associated with different therapeutic efficacy. Conclusions: The combination of Sintilimab and Axitinib showed manageable safety profile and durable anti-tumor efficacy in FH-dRCC. Evaluating mutation status of FH gene could help to predict potential survival benefit from ICI plus TKI therapy. Clinical trial information: NCT04387500 .