tbuckley/cabot-search huggingface dataset:
Amivantamab plus lazertinib vs osimertinib in first-line <i>EGFR</i>-mutant advanced non-small cell lung cancer (NSCLC) with biomarkers of high-risk disease: A secondary analysis from the phase 3 MARIPOSA study.
Authors: Enriqueta Felip, Byoung Chul Cho, Vanesa Gutiérrez, Adlinda Alip, Benjamin Besse, Shun Lu, Alexander I. Spira, Nicolas Girard, Raffaele Califano, Shirish M. Gadgeel, James Chih-Hsin Yang, Naoyuki Nogami, Koichi Azuma, Joshua C Curtin, Jiarui Zhang, Anesh Panchal, Mariah Ennis, Seema Niphadkar Sethi, Joshua Michael Bauml, Se-Hoon Lee
Journal: Journal of Clinical Oncology (2024)

8504 Background: Amivantamab (ami) is an EGFR-MET bispecific antibody with immune cell-directing activity. Lazertinib (laz) is a CNS-penetrant, 3 rd -generation EGFR TKI. In MARIPOSA (NCT04487080), first-line ami+laz provided a statistically significant improvement in progression-free survival (PFS) vs osimertinib (osi) in patients (pts) with EGFR-mutant advanced NSCLC (HR, 0.70; P&lt; 0.001), including in pts with a history of brain metastases (HR, 0.69; Cho Ann Oncol 2023;34:S1306, LBA14). Pts with TP53co-mutations, detectable circulating tumor DNA (ctDNA), and baseline brain or liver metastases have poor prognoses. We evaluated outcomes for pts in these high-risk subgroups from MARIPOSA. Methods: MARIPOSA enrolled pts with treatment-naïve, EGFR-mutant (Ex19del or L858R) advanced NSCLC. This analysis included pts randomized to ami+laz (n = 429) or osi (n = 429). Pathogenic alterations were analyzed by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and Cycle (C) 3 Day (D) 1 with Biodesix droplet digital PCR (ddPCR). Results: Baseline ctDNA for NGS analysis of pathogenic alterations was available for 636 pts (ami+laz, n = 320; osi, n = 316). Among pts with TP53 co-mutation, mPFS was 18.2 months (mo) for ami+laz vs 12.9 mo for osi (HR, 0.65; P= 0.003). Pts with TP53 wild-type had a trend favoring ami+laz for mPFS (HR, 0.75; P =0.11). In pts with ddPCR-detectable ctDNA at baseline, ami+laz significantly prolonged mPFS vs osi (20.3 vs 14.8 mo; HR, 0.68; P= 0.002). Further, ami+laz significantly improved mPFS vs osi in pts with ctDNA clearance at C3D1 (24.0 vs 16.5 mo; HR, 0.64; P= 0.004) and in pts who did not clear ctDNA (16.5 vs 9.1 mo; HR, 0.48; P= 0.014). For pts with liver metastases at baseline, ami+laz significantly prolonged mPFS vs osi (18.2 vs 11.0 mo; HR, 0.58; P= 0.017), which is consistent with the improved PFS for ami+laz vs osi in pts with a history of brain metastases. Conclusions: Ami+laz demonstrated significantly improved mPFS vs osi in pts with biomarkers of high-risk disease. Given these features can occur in up to 85% of pts, ami+laz represents an important new standard of care for treatment-naïve EGFR-mutant advanced NSCLC. Clinical trial information: NCT04487080 . [Table: see text]
Survival outcomes of patients with extensive-stage small cell lung cancer who received treatment with atezolizumab in combination with carboplatin and etoposide: A propensity score adjusted cohort study.
Authors: Heya Batah, Bridget Adcock, Monica Lee, Preeyal Patel, Meera Patel, Hadil Zureigat, Ahmed Hassan, Daniel Paul Nurse, Asad Rauf, Jacqulyn Tomer, Douglas Robert Hoen, Khaled Aref Hassan, Nathan A. Pennell, Marc A. Shapiro, James Stevenson, Emily Craig Zabor, Alex A Adjei, Moaath Khader Mustafa Ali
Journal: Journal of Clinical Oncology (2024)

8096 Background: Small cell lung cancer (SCLC) is an aggressive type of lung cancer. Most patients (pts) are diagnosed with extensive-stage disease (ES-SCLC). The cornerstone treatment of ES-SCLC has been platinum-based chemotherapy and etoposide. Combining atezolizumab with carboplatin plus etoposide (Carbo-E) improved overall survival (OS) in ES-SCLC pts and became a new standard for first-line treatment. However, there is a paucity of real-world outcomes in ES-SCLC. Herein, we present the largest and longest follow-up retrospective study analyzing atezolizumab in combination with chemotherapy for treatment of ES-SCLC. Methods: We conducted a retrospective study and included all adult pts (≥ 18 years) with ES-SCLC treated at Cleveland Clinic between 1/2010-12/2022. ES-SCLC was defined as stage IIIB or stage IV. We collected treatment regimens and baseline characteristics including age, sex, race, smoking, alcohol intake history, and comorbidities. Responses were assessed using RECIST response criteria. Both OS and progression-free survival (PFS) were calculated from treatment initiation. We used propensity score (PS) weighting and multivariable Cox proportional hazards ratio (CPH) to adjust for baseline confounding. Results: We identified 561 ES-SCLC pts who received treatment, 375 (67%) received Carbo-E and 160 (29%) received Carbo-E + Atezolizumab (Carbo-E-Atezo). The table describes the baseline characteristics of Carbo-E and Carbo-E-Atezo groups. The median follow-up was 30 months (mo) (IQR: 14 - 59). In the Carbo-E arm, 45 patients (12%) received second-line immune therapy (nivolumab +/- ipilimumab or pembrolizumab). On PS-adjusted logistic regression, pts who received Carbo-E-Atezo had a 1.1 odds ratio (95%CI: 0.85-1.43, P&gt;0.05) to respond compared to pts who received Carbo-E. There was no difference in PS-adjusted median OS between pts who received Carbo-E-Atezo (9.2 mo (95%CI: 8.1-11)) vs. Carbo-E (8.4 mo (95%CI: 7.7-9.0)) (log-rank P&gt;0.05). Similarly, there was no difference in adjusted median PFS between pts who received Carbo-E-Atezo (5.9 mo (95%CI: 5.3-6.9)) vs. Carbo-E (5.5 mo (95%CI: 4.7-5.9)) (P&gt;0.05). Using CPH model, the addition of atezolizumab to Carbo-E did not decrease mortality (Hazard Ratio: 0.84, 95%CI: 0.68-1.04, P&gt;0.05). Male gender and increasing age were predictors of worse OS (P&lt;0.05). Conclusions: Among pts with ES-SCLC, the addition of atezolizumab to the standard chemotherapy regimen of Carbo-E showed no significant difference in PFS or OS in our real-world study. [Table: see text]
Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III NSCLC (TRAILBLAZER): Efficacy, safety and feasibility of surgical conversion outcomes from a proof-of-concept, phase 2 trial.
Authors: Yi-Long Wu, Qing Zhou, Yi Pan, Xue-Ning Yang, Yanqiu Zhao, Guang Han, Qingsong Pang, Zhenfa Zhang, Qifeng Wang, Jun Yao, Hui Wang, Weihua Yang, Baogang Liu, Qixun Chen, Xianghui Du, Kaican Cai, Baosheng Li, Xiao Li, Li Song, Wei Shi
Journal: Journal of Clinical Oncology (2024)

8082 Background: Consolidation immunotherapy after chemoradiation is the standard of care for unresectable stage III NSCLC. Addition of immunotherapy-based induction treatment may further improve outcome, partly by enabling surgery. We conducted a proof-of-concept, phase 2 trial to assess neoadjuvant SHR-1701 (an anti-PD-L1/TGF-β bifunctional fusion protein) with or without chemotherapy, followed by surgery or radiotherapy in unresectable stage III NSCLC and without EGFR/ ALK alterations. Methods: Patients with MDT-assessed surgically unresectable disease were given 3 cycles of neoadjuvant SHR-1701 (30 mg/kg Q3W) with or without chemotherapy (paclitaxel 175 mg/m 2 Q3W + carboplatin AUC = 5 Q3W).Patients with PD-L1 TPS &lt; 50% received combination therapy (arm A) and those with PD-L1 TPS ≥50% were randomized (1:1) to receive combination therapy (arm B) or SHR-1701 alone (arm C). After reassessment by MDT, patients received either surgery or definitive radiotherapy (60 Gy/30 fractions) plus concurrent cisplatin (30 mg/m 2 QW), all followed by consolidation SHR-1701 for 16 cycles. The primary endpoints were post-induction objective response rate (ORR) and 18-month event-free survival (EFS) rate. Arm A+B (patients receiving neoadjuvant chemoimmunotherapy) was the primary analysis cohort. Results: Between Nov. 20, 2020 and Jan. 27, 2022, 107 patients were enrolled (arm A/B/C, n = 88/9/10). Median follow-up was 22.2 months. In arm A+B, both primary endpoints were met, with a post-induction ORR of 58% (95% CI 47-68) and an 18-month EFS rate of 56.6% (95% CI 45.2-66.5). In arm C, the post-induction ORR was 40% (95% CI 12-74) and 18-month EFS rate was 77.1% (95% CI 34.5-93.9). 24-month overall survival rate was 78.3% (95% CI 68.0-85.7) in arm A+B and 100% in arm C. Overall, 27 (25% of 107; arm A+B/C, n = 24/3) patients underwent surgery; all achieved R0 resection. Among them, 12 (44%) MPR and seven (26%) pCR were recorded. The 18-month EFS rate was 74.1% (95% CI 53.2-86.7) in resected patients and 57.3% (43.0-69.3) in those receiving radiotherapy. Across arms, all grade ≥3 TRAEs with frequency ≥10% were hematological toxicities. No new safety signals were identified. Conclusions: NeoadjuvantSHR-1701 with chemotherapy, followed by surgery or radiotherapy, showed promising anti-tumor activity with a tolerable safety profile in unresectable stage III NSCLC. We provided first evidence that surgical conversion was feasible in a notable proportion of patients, and was associated with better survival outcomes. Clinical trial information: NCT04580498 .
Lung cancer MDT quality assessment: A nationwide study.
Authors: Janna Berg, Christina Aamelfot, Siv-Gyda Aanes, Marit Wilskow, Maria Moksnes Bjaanæs, Odd Terje Brustugun, Sverre Fluge, Per Andersen Flåtten, Bjorn Henning Gronberg, Terje Skraastad, Rene P van Helvoirt, Martin Petersen, Rune Tilseth, Torben Riis Rasmussen, Kirill Neumann
Journal: Journal of Clinical Oncology (2024)

8594 Background: This observational study evaluates concordance between lung cancer multi-disciplinary team (MDT) meetings, focusing on diagnosis, staging, and treatment recommendations, especially for curative options. Assessing MDT decisions aims to identify factors potentially affecting survival rates, promoting equal treatment access for patients nationwide. Methods: In Norway, patients with lung cancer are discussed at local MDT (without a thoracic surgeon present) and at university hospital MDT (with a thoracic surgeon present). All hospitals received 35 fictitious case reports of patients with inoperable non-small cell (NSCLC) and small cell lung cancer (SCLC) with anonymized CT and PET images for discussion at the ordinary MDT meetings. Of the 12 participating hospitals, 5 were university hospitals. Results: Of the 35 patient’s cases, 12 were assessed as having stage III NSCLC. For 10 of the 12 there were differences in stage assessment, from stage IIIA-B-C to IV, and in recommended treatment (Table). For each case, curative treatment was recommended by a varying number of MDTs, from zero to nine of 12. Treatment suggestions for the four SCLC patients were identical except for one patient with stage IV, performance status (PS) score 2-3 and stroke, for whom the recommended treatment ranged from best supportive care (BSC) to triple therapy. There was generally good consensus between recommending treatment with a tyrosine kinase inhibitor (TKI) in patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) translocation positivity. We found that factors leading to discrepancies in MDT decisions were patients age &gt;75-80 years, comorbidities, PS 2 or lack of a stated PS, PD-L1 more than 50-75% in stage IV and large cell neuroendocrine carcinoma (LNEC). Conclusions: MDT-recommendations regarding treatment varied between MDT sites, and this may have the greatest consequences for patients in stage III. MDT treatment recommendations varied between the sites, confirming that treatment choice can be challenging in certain type of cases like elderly, poor PS or LNEC. Shared decision-making (SDM) with patients was often recommended. As an important outcome of the study, we found no difference in treatment choice between local and university hospital MDTs. [Table: see text]
Efficacy and safety of bronchial arterial chemoembolization (BACE) in combination with tislelizumab for non-small cell lung cancer (NSCLC): A phase II study.
Authors: Xuhua Duan, Hao Li, Donglin Kuang, Mengfan Zhang, Wenze Xu, Chao Liang, Jiacheng Wang, Daqian Han, Jianzhuang Ren
Journal: Journal of Clinical Oncology (2024)

8609 Background: Bronchial artery chemoembolization (BACE) and immune checkpoint inhibitors (ICIs) are important therapy for NSCLC. The short-term benefit from BACE is considerable while the long-term survival benefits from ICIs is remarkable. This trial is designed to determine the efficacy and safety of immunotherapy with tislelizumab in addition to BACE in stage III-Ⅳ NSCLC patients (pts) who failed, refused or ineligible to receive standard treatments. Methods: In a single-arm, phase II study (NCT05058560), stage III-IV NSCLC patients who refused or were ineligible to receive standard treatments were enrolled. Patients received BACE followed by 200 mg tislelizumab every 3 weeks until disease progression, intolerable toxicities, or discontinuation determined by the investigators. The primary endpoint was progression-free survival (PFS), and the secondary endpoints were overall survival (OS), objective response rate (ORR), disease control rate (DCR), safety, and quality of life (QoL). Results: Thirty patients were enrolled in this study between December 2021 and August 2022. The median follow-up was 12 (range, 1.5-12) months. At the data cutoff (August 31, 2023), the median PFS was 10.5 (95% confidence interval [CI], 7.8-13.2) months and the median OS was not reached. The 3 -, 6 -, and 12-month ORR were 63.3% (95%CI, 43.9%-80.1%), 56.7% (95%CI, 37.4%-74.5%), and 30.4% (95%CI, 13.2%-52.9%), respectively. The DCR at 3 months was 80% (95%CI, 61.4%-92.3%), at 6 months was 76.7% (95%CI, 57.7%-90.1%), and at 12 months was 47.8% (95%CI, 26.8%-69.4%). The expression rate of PD-L1, tumor feeding arteries, and the application times of tislelizumab were prognostic factors for PFS. No grade 3 or higher treatment-related adverse events (TRAEs) occurred. Common grade 2 TRAEs were nausea, fever, and cough. QoL improved significantly after 1 cycle of treatment compared with baseline, including global quality of life, physical functioning, and emotional functioning. Conclusions: The study demonstrated promising efficacy and manageable safety profiles of BACE plus tislelizumab for advanced NSCLC patients, indicating a potential and effective treatment option for this population. Clinical trial information: NCT05058560 .
Correlation of the combination of CT-derived tumor texture and vessel tortuosity on survival outcomes for immunotherapy but not for chemotherapy in metastatic non-small cell lung cancer (mNSCLC): Results from a CheckMate227 (CM227) subset.
Authors: Pushkar Mutha, Mohammadhadi Khorrami, Babajide Sonuga, Kshitij Aggarwal, Wiem Safta, Diederik J. Grootendorst, David Paulucci, Oana Mustatea, Brook Nepon Sixt, David Witt, Hilmi Al-Shakhshir, Vidya Sankar Viswanathan, Jeremy Callahan, Vamsidhar Velcheti, Anant Madabhushi
Journal: Journal of Clinical Oncology (2024)

8610 Background: CM227 (NCT02477826) is a large multi-center phase 3 trial that evaluated the benefit of immunotherapy (IO) over chemotherapy (Ch) as first line therapy in stage IV NSCLC. While PD-L1 and tumor mutational burden (TMB) initially emerged as promising biomarkers, CM227 showed benefit of IO over Ch regardless of PD-L1 or TMB status. There is an unmet clinical need for predictive biomarkers to identify patients (pts) who will respond to IO. In this study, we report initial blinded validation results of a CT-derived biomarker combining change in textural radiomics (Δ-Rad) and quantitative vessel tortuosity (Δ-QVT) between baseline and 6-week post-treatment for predicting response and survival outcome of IO and Ch alone in a subset of patients enrolled in CM227. Methods: This retrospective study included baseline (B) and 6-week post-treatment (TP1) CT scans from (a) a multi-center training set (D tr , N=110) of first line IO-treated mNSCLC pts and (b) a validation set consisting of a subset of mNSCLC from CM227 (D v , N=224), of which 178 pts were treated with IO (D v IO ) and 36 pts (D v Ch ) with Ch. Intra-tumoral, peri-tumoral texture radiomic (Khorrami et al., Cancer Immunol Res 2020) and QVT (Alilou et al., Sci Adv 2022) features were extracted from up to the two largest measurable lung lesions on each CT using an in-house MATLAB pipeline. Δ-Rad and Δ-QVT features were computed as the feature difference between B and TP1. A best objective IO response classifier, M Combo was trained on D tr using a combination of Δ-Rad and Δ-QVT features. Kaplan-Meier analyses with log rank p-values, hazard ratio (HR) and its confidence interval (CI) were computed to assess the predictive benefit of M Combo with overall survival (OS) and progression free survival (PFS) in D v , D v IO and D v Ch . We also report area under the receiver operating characteristic (AUC) of IO response predictions compared against best overall response in D v , D v IO and D v Ch . Results: M Combo predicted best overall response with an AUC of 0.67, 0.68, 0.74 in D v , D v IO , and D v Ch , respectively. M Combo was statistically significantly associated with OS and PFS in D v and D v IO but not in D v Ch (Table). Conclusions: Our preliminary findings reveal that combination of CT-based textural and vessel tortuosity features are predictive of IO response over chemotherapy in a subset of CM227 pts. Validation on the entire CM277 cohort is warranted. [Table: see text]
An interpretable AI-derived radiology signature to identify patients at risk of progression on the PACIFIC regimen for unresectable non-small cell lung cancer.
Authors: Omid Haji Maghsoudi, Liam IL Young Chung, Seyoung Lee, Jeeyeon Lee, Haseok Kim, Amogh Hiremath, Kai Zhang, Diego Cantor, Monica Yadav, Hye Sung Kim, Jisang Yu, Yuchan Kim, Ilene Hong, Grace Kang, Amy Cho, Yury Velichko, Vamsidhar Velcheti, Anant Madabhushi, Nathaniel Braman, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

8079 Background: Advances in the treatment of unresectable NSCLC have emerged through the combination of chemotherapy, radiotherapy, and immune checkpoint inhibitors (ICI), also known as the PACIFIC regimen. Despite this protocol’s benefits, it lacks predictive biomarkers and many patients will ultimately fail to respond. Artificial intelligence (AI) has shown promise in identifying patients responsive to ICI, but its ability to identify patients who may not benefit from such combination regimens remains underexplored. We introduce an AI-enabled approach leveraging interpretable imaging biomarkers, such as tumor heterogeneity and twistedness of the tumor-associated vasculature, to identify patients who will fail to benefit from chemo-radio-immunotherapy (CRIT) using pretreatment scans. Methods: We analyzed CT data from 148 NSCLC patients with predominantly stage III (91%) disease from two institutions. Target lesions were delineated by a trained radiologist. The Picture Health Px platform was utilized to segment the lungs and pulmonary vessels. Subsequently, a number of interpretable imaging features from the tumor and surrounding tissues were extracted. A Cox proportional hazards model of feature clusters was developed on the training set (n = 101) to stratify patients into benefit groups associated with progression-free survival (PFS). A cohort of 47 patients receiving CRIT were held out for testing. Results: The imaging-derived high-risk group defined by the model was associated with decreased PFS in the test set, with a hazard ratio (HR) of 4.99 (95% CI: 2.04-12.18; p &lt; 0.005) and concordance index (C-index) of 0.66. The risk groups identified by the model outperformed PD-L1 negative status in identifying likely progressors (C-index = 0.52; HR = 1.49 [0.51-4.54], p = 0.47), and were additionally independently prognostic of PD-L1 status when compared in a multivariable analysis (p &lt; 0.001). The primary features driving the model were measurements of the radius and tortuosity of the tumor-associated vasculature, as well as heterogeneity metrics of the tumor. Conclusions: An AI imaging tool that stratifies patients by risk after CRIT from baseline radiology was developed. The tool was able to strongly identify a subset of patients at very high risk of progression if treated with CRIT. These risk groups outperformed PD-L1 and thus may address biomarker gaps in the CRIT setting. With further clinical validation, radiology-based risk stratification could be used to identify a subset of unresectable NSCLC patients for whom alternatives to the standard of care should be explored.
Amivantamab plus chemotherapy vs chemotherapy as first-line treatment among patients with EGFR exon 20 insertion–mutated advanced non-small cell lung cancer (NSCLC): PAPILLON Chinese subgroup analysis.
Authors: Ke-Jing Tang, Baogang Liu, Yu Yao, Yanqiu Zhao, Jianying Zhou, Ping Sun, Donglin Wang, Dongqing Lv, Huijie Wang, Yi Hu, Qiang Li, Yujiao Song, Grace Gao, Liyun Wang, Trishala Agrawal, Archan Bhattacharya, Mahadi Baig, Patricia A Lorenzini, Honeylet Wortman-Vayn, Caicun Zhou
Journal: Journal of Clinical Oncology (2024)

8606 Background: Amivantamab (Ami) is a bispecific antibody targeting EGFR and MET tyrosine kinase receptors with immune cell-directing activity. The phase 3 PAPILLON study (NCT04538664) investigated the combination of Ami and carboplatin/pemetrexed (ACP) vs. carboplatin/pemetrexed (CP) as first-line treatment in patients (pts) with advanced EGFR Exon20ins-mutated NSCLC. ACP improved progression free survival (PFS) in both the overall population and Asian subgroup. Methods: Pts were randomized 1:1 to ACP or CP. The primary endpoint was PFS by blinded independent central review (BICR) and key secondary endpoints included objective response rate (ORR), PFS after first subsequent therapy (PFS2), overall survival (OS), and safety. Crossover to Ami monotherapy was allowed for pts in CP arm following disease progression. Results: Among the 308 pts enrolled, 87 were Chinese, with 39 receiving ACP and 48 receiving CP. Median age was 57/57 years, 46%/63% were female, and 15%/25% history of brain metastases for pts in ACP/CP arms. Baseline characteristics were generally balanced between arms. After a median follow-up of 16.4 months (mo), median PFS was 12.3 mo (95% CI: 7.00, NE) in ACP arm compared with 6.7 mo (95% CI: 4.21, 8.57) in CP arm (hazard ratio [HR], 0.47; 95% CI, 0.26-0.85; P = 0.011) (Table). ORR was 71.8% (95% CI, 55.1%-85.0%) for ACP, and 48.9% (95% CI, 34.1%–63.9%) for CP (odds ratio, 2.46; 95% CI, 1.01-5.98; P = 0.048). Median PFS2 was not estimable (NE) for ACP vs 18.8 mo for CP (HR, 0.32; 95% CI, 0.11-0.88; P = 0.021). Interim OS showed a favorable trend for ACP vs CP (HR, 0.58; 95% CI: 0.17-2.02; P = 0.387) despite crossover among CP-randomized pts (n = 24, 50%) who had progressed. Most common AEs (all grades) ( &gt; 50%) in ACP arm were rash, paronychia, hypoalbuminemia, neutropenia, anemia, leukopenia and thrombocytopenia which were consistent with the known safety profile of the individual agents. Notably, no pts had discontinuation of Ami due to an AE. Conclusions: ACP demonstrated superior PFS compared to CP in Chinese pts. The safety profile was manageable and tolerable. These findings in Chinese subgroup were consistent with those of overall population and Asian subgroup. Clinical trial information: NCT04538664 . [Table: see text]