tbuckley/cabot-search huggingface dataset:
Efficacy and safety of lurbinectedin (LUR) with irinotecan (IRI) in patients (Pts) with relapsed small cell lung cancer (SCLC): Results from a phase 2 expansion cohort.
Authors: Luis G. Paz-Ares, Alejandro Falcon Gonzalez, Alejandro Navarro, Amparo Sanchez-Gastaldo, Gregory Michael Cote, Bruno Bockorny, Javier Molina-Cerrillo, Angel Artal, Javier Baena, Ana Gil, Santiago Ponce Aix, Helena Bote de Cabo, Sara Martinez, Julia Martinez Martinez, Jose Antonio Lopez-Vilariño, Carmen Maria Kahatt, Ali Hassan Zeaiter, Javier Gomez, Jon Zugazagoitia
Journal: Journal of Clinical Oncology (2024)

8094 Background: LUR has been approved in the US and elsewhere for treatment of adult pts with metastatic SCLC and disease progression on or after platinum-based chemotherapy. Preclinical studies found synergy for LUR with IRI (Galmarini C. Cancer Res 2013; 73: Abst 5499). The phase 1b/2 study PM1183-A-014-15 (NCT02611024) evaluated the LUR/IRI combination in pretreated pts with advanced solid tumors. The phase 1b part defined the recommended dose at LUR 2.0 mg/m 2 on Day (D)1 + IRI 75 mg/m 2 on D1,D8 every three weeks with primary G-CSF prophylaxis, and found promising results for the combination in SCLC pts after first-line therapy (Ponce Aix S. Ann Oncol 2019; 30: Abst 471P). Methods: Eligibility criteria for this cohort of the phase 2 part of this study included: confirmed SCLC, progression after one platinum-containing regimen, controlled brain metastases and ECOG PS ≤ 1. The primary endpoint was overall response rate (ORR). Results: 101 evaluable pts were enrolled. Baseline characteristics included: median age 63 (range, 45-77 y), 60.4% males, 76.2% ECOG PS 1, 28.7% CNS involvement, 39.6% bulky disease and 41.6% pretreated with immunotherapy. Chemotherapy-free interval (CTFI) was &lt;90 d in 51.4% of pts (26.7% had CTFI&lt;30 d. Median CTFI was 85 d (range, 0-323 d). Median number of cycles per pt was 6 (range, 1-34); 25.7% received &gt;10 cycles. Efficacy results by independent review committee are summarized in the table. Treatment-related adverse events (AEs) were observed in 99.0% of pts (grade ≥3 in 69.3%). Most relevant grade ≥3 events/abnormalities were neutropenia (52.5%), anemia (27.7%), diarrhea (19.8%), fatigue (18.8%), and febrile neutropenia (9.9%). Treatment-related SAEs occurred in 25.0% of pts and 5.0% discontinued due to treatment-related AEs. No treatment-related deaths occurred. Conclusions: The LUR/IRI combination showed promising antitumor activity and a manageable safety profile in these pts with poor prognosis, particularly those with CTFI&gt;30 d. These encouraging results reinforce the rationale for including this combination as an experimental arm in the ongoing pivotal phase 3 LAGOON trial (NCT05153239) in relapsed SCLC with CTFI&gt;30 d. Clinical trial information: NCT02611024 . [Table: see text]
Intracranial efficacy of datopotamab deruxtecan (Dato-DXd) in patients (pts) with previously treated advanced/metastatic non-small cell lung cancer (a/m NSCLC) with actionable genomic alterations (AGA): Results from TROPION-Lung05.
Authors: Aaron Lisberg, Myung-Ju Ahn, Satoru Kitazono, Byoung Chul Cho, George R. Blumenschein, Elaine Shum, Elvire Pons-Tostivint, Yasushi Goto, Kiyotaka Yoh, Luis G. Paz-Ares, Rebecca Suk Heist, Paul Baas, David Planchard, Maurice Perol, Enriqueta Felip, Wu-Chou Su, Hong Zebger-Gong, Lan Lan, Chelsea Liu, Jacob Sands
Journal: Journal of Clinical Oncology (2024)

8593 Background: Brain metastases (mets) occur frequently in pts with NSCLC, particularly pts with certain AGAs, and indicate poor prognosis. For pts with AGAs, treatment options are limited once targeted therapy and platinum-based chemotherapy (Pt-CT) become ineffective. The phase 2 TROPION-Lung05 trial (NCT04484142) of Dato-DXd has demonstrated systemic efficacy and a manageable safety profile in heavily pretreated pts with a/m NSCLC with AGAs who progressed following targeted therapy and Pt-CT; here we report an exploratory analysis of intracranial (IC) efficacy. Methods: Pts were treated with Dato-DXd 6 mg/kg IV Q3W. Pts with clinically stable brain mets were eligible. IC responses were assessed by blinded independent central review (BICR) of cranial CT/MRI (CNS BICR; per CNS RECIST) at baseline (BL) and Q6W. Systemic objective response rate (ORR), disease control rate (DCR), clinical benefit rate (CBR, defined as CR+PR+SD or non-CR/non-PD lasting ≥6 mo), progression-free survival (PFS) by BICR per RECIST 1.1 and treatment-related adverse events (TRAEs) were determined in pts with and without BL brain mets. Results: In total 53/137 (39%) treated pts had BL brain mets; 29/53 (55%) had an EGFRmutation. Pts with BL brain mets had a median (range) of 3 (2–6) prior systemic therapies in the a/m setting, including targeted therapy and Pt-CT with/without immune checkpoint inhibitors; 15/53 (28%) had untreated brain mets. At data cutoff (Dec 14, 2022), median (range) study and treatment durations among pts with BL brain mets were 14.8 (9.7–20.5) and 3.2 (0.7–17.2) mo, respectively. Of these pts, 18/53 (34%) had measurable IC target lesions (3 untreated) and 35/53 (66%) had only non-target IC lesions. In 18 pts with target lesions, IC ORR was 22% (95% CI, 6–48), including 1 of 3 pts with untreated target lesions; IC DCR was 72% (95% CI, 47–90); IC CBR was 44% (95% CI, 22–69). Reduction in the sum of diameters of brain lesions was seen in 10/18 (56%). Median time to IC response was 1.5 (range, 1.3–5.4) mo; median duration of IC response was 5.5 (95% CI, 3.4–NE) mo Systemic efficacy and safety were similar in pts with and without BL brain mets (Table). Conclusions: Dato-DXd showed encouraging IC activity consistent with systemic responses in pts with a/m NSCLC with AGAs, supporting further investigation of Dato-DXd in pts with brain mets. Clinical trial information: NCT04484142 . [Table: see text]
Practice makes perfect: Using simulation to build and assess competency in bone marrow biopsy for heme/onc fellows.
Authors: Lori J. Rosenstein
Journal: Journal of Clinical Oncology (2024)

9042 Background: The American Board of Internal Medicine (ABIM) requires that Hematology/Oncology fellows demonstrate competence in bone marrow biopsies (BMB). However, offers no guidance in assessment methods. Neither the "see one, do one, teach one" nor the "complete 5 procedures" approach is sufficient to ensure competency. As this is a potentially painful procedure that requires knowledge of landmarks, simulation in a safe environment is an ideal way to introduce BMB to trainees. In 2015, we started a simulation program to teach fellows how to perform BMB using a cadaver pelvis, and assess their BMB competency. Methods: The Hematology Oncology Fellowship Program at Gundersen Health System holds a half-day simulation for our 6 fellows each July. We begin with a self-evaluation of current skills, using an 8-question pre-test. We then view a demonstration video, pausing to discuss key learning points. Fellows are given a detailed check list of the steps of the procedure. They then experiment with the tools of the procedure and practice sterile technique. We discuss the indications, contraindications, consent, and the procedure itself. For part two, fellows are divided into two groups, each consisting of a first year (F1), second year (F2), and third year (F3) fellow. A cadaver pelvis is used as the model and is positioned in a prone position. Each team is assigned a side of the pelvis. The F3 demonstrates the procedure from start to finish while the F2 and staff assesses competency and the F1 follows with the procedure check list. Once the F3 has completed the procedure and is deemed "competent" they become the leader of the session for their team. F1s can practice as many times as desired, under the guidance of the F2 and F3. F2s also have a chance to refine their skills. After the simulation is complete, fellows repeat the self-evaluation, and we debrief. Results: 44 fellows completed the simulation (F1=16, F2=14, F3=14). Questions for the pre- and post-tests were ranked on a 5-point Likert Scale of strongly agree (1) to strongly disagree (5). F1s had the worst self-assessment prior to the procedure, with a mean score of 2.4 for all questions. However, their post-test self-assessment improved to 1.6. F2s started at 1.5 and improved to 1.1 after the simulation. F3s started at 1.2 and improved to 1.0. All fellows answered that this was a useful exercise and should be continued. Comments were consistently positive, speaking to the importance of a check list, the relaxed atmosphere, and having senior fellows teach the junior fellows. Conclusions: BMB simulation allows for a low-stakes introduction to a stressful procedure, while promoting a team approach to learning. It also gives an opportunity to verify competence for graduating fellows. Fellows self-reported improvement following the session as well as from year to year. Fellows value this learning experience and look forward to it each year.
Time toxicity for patients receiving oral versus parenteral hypomethylating agents for myelodysplastic syndromes/neoplasms (MDS).
Authors: Robert S Epstein, Amer Methqal Zeidan, Abisola Olopoenia, Halley Costantino, Kushal Modi, Tehseen Salimi, Terri Washington, JoAnn Krenitsky
Journal: Journal of Clinical Oncology (2024)

6568 Background: Patients spend substantial time receiving cancer care. Patients with higher-risk MDS treated with hypomethylating agents (HMAs) are generally older and have a median life expectancy of 11–17 months. Patients receiving parenteral treatment for MDS spend significant time in clinics receiving HMA treatment; as such, information on the time burden of treatments (“time toxicity”) is needed to help clinicians guide patients and caregivers with alternative routes of administration. The development of oral HMA therapies offers a strategy that mitigates the time toxicity associated with MDS treatment by increasing the number of “home days” for patients. This study details the time burden among patients with MDS receiving oral HMA therapy versus those receiving intravenous and subcutaneous (IV/SC) HMAs. Methods: This was a retrospective analysis of adult patients with MDS initiating HMA therapy (oral or IV/SC HMA), using the US Cerner Enviza claims database (08/2020–08/2022). Propensity score matching (1:1) was performed on the treatment groups to balance confounding factors; matched cohorts were analyzed (N=158 each). The total direct healthcare encounter days for oral and IV/SC HMA administered patients were evaluated based on the number of healthcare encounter days spent on parenteral HMA administration (0 days for oral HMAs), outpatient, inpatient, and emergency room (ER) visits, and infusion days. Only distinct encounter days were included in the total count; multiple visits in a day were de-duplicated. Mean (SD) healthcare days for oral versus IV/SC HMA groups were calculated for each type of healthcare encounter and summarized. Results: Patients receiving oral HMA incurred a mean total of 15.2 healthcare encounter days compared with 32.8 days for those receiving IV/SC HMAs (Table). Most encounter days for the oral HMA cohort were in the outpatient setting (34.9%) while most encounters for the IV/SC HMA cohort were attributed to receiving parenteral HMA administration (55.5%), followed by inpatient (16.2%) and outpatient visits (14.9%). Conclusions: This study, which is the first report to date of time toxicity in MDS among patients treated with HMA therapy, revealed that patients receiving oral HMA incurred half the time burden of those receiving IV/SC HMAs. Further research is warranted to validate these results in a larger patient cohort and compare these findings with other cancer therapies. [Table: see text]
Lorlatinib in TKI naïve, advanced ROS1-positive non-small-cell lung cancer: A multicenter, open-label, single-arm, phase 2 trial.
Authors: Beung Chul AHN, Yu Jung Kim, Dong-Wan Kim, Ki Hyeong Lee, Youngjoo Lee, Ji-Youn Han
Journal: Journal of Clinical Oncology (2024)

8519 Background: ROS1 rearrangement is rare but an attractive therapeutic target in advanced non-small cell lung cancer (NSCLC). Currently, crizotinib, entrectinib, and reprotrectinib have been approved for ROS1-positive NSCLC. Lorlatinib is a potent, brain-penetrant, third-generation tyrosine kinase inhibitor (TKI) that targets ROS1 as well as ALK. We investigated the antitumor activity and safety of lorlatinib in TKI naïve, advanced ROS1-positive NSCLC. Methods: This is a prospective multi-center, single-arm, phase II study. We enrolled TKI-naïve patients with histologically or cytologically confirmed advanced ROS1-positive NSCLC with an Eastern Cooperative Oncology Group performance status of 2 or less, and who had previously received one or no platinum-based chemotherapy. Lorlatinib 100mg once daily was given orally in continuous 21-day cycles until investigator-determined disease progression, unacceptable toxicity, withdrawal of consent, or death. The primary endpoint was an objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), and safety. For sample size calculation, we used a two-stage design to evaluate the null hypothesis (40%) and the alternative hypothesis (60%), with type I error (α) level of 10% and type II error (β) of 0.20. This study is registered in ClinicalTrials.gov, NCT03612154. Results: Between June 03, 2019, and April 26, 2023, 32 patients with ROS1-positive NSCLC were enrolled. The median age was 60, 63% were female, and all of them (100%) had adenocarcinoma histology. Twenty-one (66%) of 32 patients were treatment-naive, and 11 (34%) had previously received a platinum-based chemotherapy. The estimated median duration of follow-up for response was 15.6 months (Interquartile Range [IQR], 10.3–30.4). Twenty-two (69%; 95% confidence interval [CI], 52 to 83) patients had objective responses. The median PFS and OS were 35.8 months (95% CI, Not Reached [NR] to NR) and NR, respectively, for all patients. Regarding the previous therapy, the ORR and PFS of treatment naïve and previously treated patients were 81% vs 46% (p = 0.042) and NR vs 13.9 months (p = 0.25), respectively. The most common 3–4 grade treatment-related adverse events were hypertriglyceridemia (8 [25%] of 32 patients) and hypercholesterolemia (5 [16%]). No treatment-related deaths were reported. Conclusions: Lorlatinib showed durable clinical activity in patients with TKI naïve, advanced ROS1-positive NSCLC including those with CNS metastases. Adverse events were mainly of low grade and compatible with long-term administration. Due to its limited treatment options, lorlatinib could be integrated into an earlier stage of treatment for ROS1-positive NSCLC. Clinical trial information: NCT03612154 .
Clinical-genomic characteristics in patients with EGFR-mutated non-small cell lung cancer harboring MET copy number gains after progression on EGFR-TKI: A report from LC-SCRUM-TRY.
Authors: Tsuyoshi Hirata, Hiroki Izumi, Shingo Matsumoto, Kazumi Nishino, Terufumi Kato, Masahiro Kodani, Kenichi Chikamori, Yukio Hosomi, Satoshi Hara, Yosuke Kawashima, Shoichi Kuyama, Yuji Shibata, Hibiki Udagawa, Tetsuya Sakai, Eri Sugiyama, Kaname Nosaki, Yoshitaka Zenke, Shigeki Umemura, Kiyotaka Yoh, Koichi Goto
Journal: Journal of Clinical Oncology (2024)

8628 Background: MET amplification (amp) account for 10-15% of resistance mechanism in EGFR-mutated non-small cell lung cancer (NSCLC) to EGFR-tyrosine kinase inhibitor (TKI) treatment. MET copy number (CN) gains consists of MET focal amp and polysomy (poly), but the clinical characteristics and outcome of EGFR-TKI resistant NSCLC patients harboring MET amp, poly remains unclear. Methods: The clinical-genomic characteristics and treatment outcome ofEGFR-TKI resistant EGFR-mutated NSCLC registered in LC-SCRUM-TRY (UMIN000041957) were analyzed. Genetic resistant alterations were screened using next-generation sequencing (NGS) (Tissue; Oncomine Precision Assay [OPA] or Plasma; Guardant360 [G360]), and MET-fluorescence in-situ hybridization (FISH). MET amp was defined as MET CN ≥4 (OPA), MET CN ≥2.12 (G360) or MET/CEP7 ratio ≥2 (FISH). MET poly was defined as MET CN≥5 and MET/CEP7 ratio &lt;2 by FISH. Results: A total of 1559 patients had been enrolled in LC-SCRUM-TRY between Sep 2020 and Jan 2024. Of 1537 analyzed samples, 666 (43%) were EGFR-TKI resistant samples. Of these, 92 (14%), 239 (36%) and 335 (50%) had MET amp, poly, and no CN gain (no CNG), respectively. Patient characteristics and treatment outcome with 1 st line EGFR-TKI and platinum-based chemotherapy (PBC) post EGFR-TKI is summarized (Table 1). The overall response rate (ORR) of PBC post EGFR-TKI in the patients with MET amp, poly and no CNG was 41%, 29% and 31%, respectively (p=0.34), with median progression-free survival (mPFS) being 5.7 months, 6.8 months, and 6.7 months (p=0.02). In addition, 12 and 11 of patients with MET amp and poly were enrolled into clinical trial of MET-targeted therapy (MET-TKI, n=2; MET-antibody-drug conjugate [ADC], n=4; EGFR/MET-antibody, n=2), and MET non-targeted therapy (EGFR-TKI, n=5; other ADCs, n=10: immunotherapy; n=1). The ORR of MET-targeted therapy/MET non-targeted therapy were 60/0% for MET amp, and 0/33% for MET poly, respectively. Conclusions: Patients with shorter PFS with prior 1 st line EGFR-TKI are more likely to have MET amp. The efficacy of standard PBC post EGFR-TKI in patients with MET CNG is limited. Current MET-targeted therapy may not be effective for EGFR-mutated NSCLC harboring MET poly after progression on EGFR-TKI. [Table: see text]
Detection of comprehensive oncogenic driver alteration of non-small cell lung cancer from cytology specimens by multi-gene PCR panel.
Authors: Tetsuya Sakai, Hiroki Izumi, Shingo Matsumoto, Hibiki Udagawa, Yu Tanaka, Eri Sugiyama, Shigeki Umemura, Yoshitaka Zenke, Kiyotaka Yoh, Koichi Goto
Journal: Journal of Clinical Oncology (2024)

8579 Background: The analysis of the next-generation sequencing (NGS) panel test requires a sufficient amount of tissue specimens (TS), but the collection of tissue specimens can be sometimes challenging in clinical practice. Despite being easier and safer to collect than TS, cytology specimens (CS) are considered unsuitable for NGS due to the small number of tumor cells. The AmoyDx Pan Lung Cancer PCR Panel (AmoyDx), a multi-gene PCR panel that amplified mutation or fusion variants of 11 genes (EGFR, ALK, ROS1, RET, MET HER2, BRAF, KRAS, and NTRK1-3) by real-time PCR, can be performed with smaller amounts of nucleic acid than NGS, and CS may be suitable for multi-gene analysis using this panel. In this study, we evaluated the feasibility of multi-gene analysis using CS, and the concordance rate of gene alteration between CS and TS in non–small cell lung cancer (NSCLC). Methods: We enrolled consecutive NSCLC patients obtaining CS through bronchoscopy, including transbronchial brushing (TBB) and transbronchial needle aspiration (TBNA) from September 2020 to March 2023. These CS were preserved as frozen pellets. The difference in the amount of nucleic acid, the success rate and the concordance rate of gene alteration with AmoyDx were evaluated between CS and pared TS collected simultaneously with CS. Results: A total of 131 (Ad/Sq/NSCLC-NOS: 113/2/16) cases were enrolled in this study. Fifty-nine specimens were obtained through TBB and another 72 were obtained through TBNB. The median nucleic acid concentration (NanoDrop [ng/μL]) isolated from CS was comparable to that isolated from TS (DNA 114/99, p=0.96; RNA 36/27, p=0.63). However, the median DNA concentration in CS was significantly lower (80/102, p=0.01) in TBB samples, while in TBNA samples, it was higher (134/90, p=0.03). Almost all CS (99.2%,130/131) and TS (99.2%,130/131) were analyzed successfully with AmoyDx, with only one RNA analysis failure in each group. Among CS, 78 (60%) samples exhibit gene alteration, including EGFR/KRAS/BRAF/HER2/ALK/ROS1/MET/RET: 44/9/2/5/8/1/8/1, while 77 (59%); 44/9/2/6/6/1/8/1 in TS. The positive percent agreement, negative percent agreement, and overall percent agreement of CS using analysis compared with the results of TS using analysis were 99% (76/77), 96% (52/54), and 98% (128/131), respectively. Conclusions: CS exhibit an extremely high success rate for multi-gene analysis, with nucleic acid yield comparable to TS. Moreover, the concordance rate of gene alteration between CS and TS is also remarkably high. CS emerge as a viable alternative to TS for analyzing driver gene alteration in multi-gene PCR analysis.
The role of pulmonary metastasectomy for non-primary lung cancer: Umbrella review of meta-analysis.
Authors: Wongi Woo, Brandon Park, Awranoos Ahadi, Liam IL Young Chung, Chan Mi Jung, Ankit Bharat, Young Kwang Chae
Journal: Journal of Clinical Oncology (2024)

8639 Background: Lungs are the most common metastatic area for many cancers. Due to heterogeneous characteristics of primary cancers, the benefit of pulmonary metastasectomy (PM) has not been investigated other than colorectal cancers. Furthermore, well-designed trials in this field are difficult to undertake due to diverse clinical scenarios and therapy related to primary cancers. This study aims to investigate the clinical outcomes of PM for non-primary lung cancer by synthesizing existing literature. Methods: A systematic search for meta-analyses on PM for non-primary lung cancers was conducted, encompassing publications up to January 3, 2024. The analysis included eight primary cancer types: colorectal, renal cell, breast, adrenocortical, head and neck cancers, melanoma, and sarcoma. Primary outcomes, overall survival, and recurrence rates post-PM were assessed using random-effect models to account for study heterogeneity. Subgroup analysis categorized the survival rates based on primary cancer types, and a proportion meta-analysis was performed for comparison. Results: This study included 44 systematic-review articles and 157 individual studies, involving 23,694 patients who underwent PM for non-primary lung cancer. Patients had a mean age of 48.0 [95% CI 43.9-52.0] years, with 68.4% [95% CI 65.0-71.7] being male. About half of patients (47.1% [95% CI 40.8-53.5] had multiple metastatic lesions and 26.6% had bilateral involvement of lung. Sublobar resection was mostly performed (82%), and complete R0 resection was achieved in 87.2% [95% CI 83.0-90.8]. The pooled 5-year overall survival rate after PM was 41.2% [95% CI, 37.1-45.4%], with specific rates for each primary cancer type listed (Table). Patients with germ cell tumor demonstrated significantly higher survival rate than other cancers (p&lt;0.05), while patients with melanoma had worst outcome (p&lt;0.05). During follow-up, 57.6% [95% CI 46.4-68.1] had recurrence: 48% of them had intrathoracic only recurrence and 52% had extra-thoracic recurrence. Conclusions: The findings affirm that PM yields survival benefit. Overall survival rates following PM do not significantly differ based on primary cancer types, except for germ cell tumors and melanoma. Additionally, the recurrence rates are comparable to that of stage 4 advanced cancers other than germ cell tumor and is not significantly influenced by the primary cancer type. This highlights the importance of recognizing and incorporating PM in clinical practice when appropriate. [Table: see text]