bluuebunny/crossref_metadata_2025_split huggingface dataset:
Treatment at twilight: Is less more in the management of octogenarians with non-small cell lung cancer (NSCLC)?
Authors: Burns Ethan , Mathur Sunil , Kieser Ryan Blair , Chen Wan Hsiang , Bernicker Eric 
Published: June 2023

9042 Background: Treatment of advanced/metastatic NSCLC in older patients is hindered by performance status, comorbidities, and treatment toxicities. Moreover, whether multiagent chemotherapy in combination with immune checkpoint inhibitor (ICI) therapy outweighs a conservative approach is controversial. This study aims to assess treatment patterns and outcomes in patients ≥80 years with NSCLC through data provided by the national cancer database (NCDB). Methods: Adults ≥80 years with stage III/IV NSCLC, available treatment data, and diagnosis between 2015-2018 were included. Patients were stratified by therapy including none, ICI alone, chemotherapy alone, and chemotherapy+ICI; radiation and surgical management was also assessed. Median overall survival (OS) was evaluated by Kaplan-Meier survival methods, and differences were assessed by hazard ratios (HR) and 95% confidence intervals (CI). The mean difference in OS was compared between systemic therapy arms. Pearson Chi-Squared tests assessed the significance of treatment differences, with a p-value of < 0.05 considered statistically significant. Results: There were 42,356 patients included; 29,698 (70.1%) had stage IV disease and 26,314 (62.1%) had adenocarcinoma. A total of 3,248 (7.7%) received ICI, 11,505 (27.2%) received chemotherapy, 2,393 (5.6%) received chemotherapy+ICI, and 25,210 (59.5%) received no therapy. Median OS for no therapy, ICI, chemotherapy, and chemotherapy+ICI was 2.63 (95% CI: 2.57, 2.69), 10.68 (95% CI: 9.96, 11.39), 12.35 (95% CI: 11.98, 12.72), and 14.03 (95% CI: 13.87, 14.88) months, respectively. Compared to no therapy, ICI alone (HR: 0.377 [95% CI: 0.361, 0.393], p = 0.000), chemotherapy alone (HR: 0.439 [95% CI: 0.426, 0.452], p = 0.000), and chemotherapy+ICI (HR: 0.345 [95% CI 0.328, 0.363], p = 0.000) improved OS. Compared to ICI, chemotherapy and chemotherapy+ICI had a longer mean OS difference of 2.48 (95% CI 1.82, 3.13) (p < 0.001) and 1.9 (95% CI 1.01, 2.78 (p < 0.001) months, respectively. In chemotherapy alone, the median OS was 1.12 months (95% CI: 0.55, 1.70) (p < 0.001) longer with multiagent vs single agent. There was no difference between chemotherapy vs chemotherapy+ICI (0.57 months [95% CI: 0.16, 1.31], p = 0.234), or for ICI+single agent vs ICI+multiagent (0.67 months [95% CI -1.18, 2.54], p = 1.00). Treatment with radiation (HR: 0.664 [95% CI: 0.649, 0.679], p < 0.001), primary-sit(HR: 0.495 [95% CI: 0.465, 0.527], p < 0.001) and non-primary surgery (HR: 0.867 [95% CI: 0.811, 0.927], p < 0.001), and receipt of ICI vs no ICI (HR: 0.912 [95% CI 0.873, 0.954], p < 0.001) improved OS. Conclusions: Patients ≥80 years with NSCLC derived most benefit from multiagent chemotherapy or chemotherapy+ICI, with no OS difference between ICI+single or ICI+multiagent therapy. ICI alone and no therapy had inferior OS. Future trials to corroborate this finding would benefit the elderly population.
Factors impacting outcomes in individuals ≥80 years with non-small cell lung cancer (NSCLC): A national cancer database (NCDB) analysis.
Authors: Burns Ethan , Mathur Sunil , Kieser Ryan Blair , Chen Wan Hsiang , Bernicker Eric 
Published: June 2023

9043 Background: Older individuals with advanced/metastatic NSCLC have inferior outcomes compared to younger patients. Aside from baseline comorbidities and treatment-limiting toxicities, identifying factors that impact overall survival (OS) in this population is needed. The aim of this study is to assess characteristics impacting outcomes in patients ≥80 years with NSCLC using the NCDB. Methods: Adults ≥80 years with NSCLC, stage III/IV disease, diagnosed between 2015-2018, and available demographic data were included. Age, sex, race, insurance status, hospital subtype, Charelson-Deyvo comorbidity (CDCC) index, cancer stage (III/IV), geographic region in the United States (US), and histologic NSCLC subtypes were compared. Kaplan-Meier methodology assessed differences in median OS, and differences were compared using hazard ratios (HR) with 95% confidence intervals (CI). Pearson Chi-Squared test assessed the significance of covariates, and a p value < 0.05 was considered statistically significant. Results: There were 42,356 patients included. Median age was 83 (80-90) years, 20,422 were (48.2%) female, 35,653 (84.2%) were white, 37,738 (89.1%) had medicare coverage, 11,055 (26.1%) received treatment at an academic hospital, and 14,383 (33.9%) received care in the southern United States. Treatment at an academic hospital (HR: 0.91 [95% CI: 0.87, 0.95], p < 0.001), females (HR: 0.82 [95% CI 0.81, 0.84], p < 0.001), Medicaid (HR: 0.77 [95% CI: 0.65, 0.93], p = 0.005) vs no insurance, and adenocarcinoma (HR: 0.79 [95% CI: 0.74, 0.84], p < 0.001) or squamous cell carcinoma (HR: 0.84 [95% CI: 0.80, 0.90, p < 0.001] had better outcomes. Patients in the Northeastern (HR: 0.90 [95% CI: 0.87, 0.93], p < 0.001), Southern (HR: 0.92 [95% CI: 0.89, 0.94], p < 0.001), and Western (HR: 0.89 [95% CI: 0.88, 0.93], p < 0.001) US had better OS compared to the Midwest. Compared to whites, patients who were black (HR: 0.92 [95% CI: 0.88, 0.85], p < 0.001), Asian (HR: 0.77 [95% CI: 0.72, 0.82], p < 0.001), Hispanic (HR: 0.83 [95% CI: 0.78, 0.88], p < 0.001), or other (HR: 0.88 [95% CI: 0.79, 0.97) had better outcomes. Per year increase in age (HR 1.009 [95% CI: 1.006, 1.013], p < 0.001), patients with CDCC score of 1 (HR: 1.16 [95% CI: 1.14, 1.19], p < 0.001), 2 (HR: 1.22 [95% CI: 1.18, 1.27], p < 0.001), and ≥3 (HR: 1.33 [95% CI: 1.284, 1.380], p < 0.001) vs 0, and stage IV NSCLC (HR: 1.83 [95% CI: 1.79, 1.88], p = 0.000) had poorer survival. Conclusions: White race, males, uninsured status, receipt of treatment in the Midwest, community hospital treatment, large cell histology, advancing age, stage IV disease, and increasing CDCC score all had poorer outcomes in adults ≥80 years with advanced NSCLC. These factors should be taken into consideration when discussing the diagnosis, management, and expectations of the disease course with patients in the geriatric age group.
Role of immunotherapy in stage IV non-small cell lung cancer with liver metastasis: A NCDB analysis.
Authors: Komiya Takefumi , Takamori Shinkichi 
Published: June 2023

9046 Background: Despite approvals of immune checkpoint inhibitors in stage IV non-small cell lung cancer (NSCLC), survival benefit of immunotherapy (IO) in those with liver metastasis is controversial. Randomized controlled trials demonstrated conflicting results. Methods: Using National Cancer Database (NCDB), Stage IV NSCLC cases diagnosed in 2016-2017 with at least 30-day follow up were analyzed. Clinical demographics included age (20-69 vs. 70+), sex (male vs. female), race (whites vs. others), institution (academic vs. others), Charlson-Deyo score (0-1 vs. 2-3), year of diagnosis (2016 vs. 2017), Histology (adenocarcinoma NOS vs. other), brain metastasis (Yes vs. No), bone metastasis (Yes vs. No), liver metastasis (Yes vs. No). They were divided into liver-metastasis positive (LM+) vs. negative (LM-). Information regarding cancer treatment was limited to the first course of therapy, including surgery for primary lesion (Yes vs. No), radiation (Yes vs. No), multi-agent chemotherapy (Yes vs. No), and IO (Yes vs. No). Overall Survival (OS) analysis was performed using Kaplan-Meier curves and Log-rank tests. Cox proportional hazard model was used for multivariate analyses. A two-sided p-value < 0.05 was considered as significant. Results: A total of 13,594 LM+ and 69,885 LM- cases met eligibility and further analyzed. 2,944 and 15,553 patients were treated with IO, respectively. No significant association between use of IO and status of liver metastasis was observed (p = 0.124). The median OS in LM+ cases was significantly shorter than that in LM- cases (5.0 vs 8.8 months, respectively, p < 0.0001). Use of IO was associated with improved OS in both LM+ and LM- cohorts with similar HRs/p-values (0.62/ < 0.0001 and 0.64/ < 0.0001, respectively). Multivariate analysis demonstrated that use of IO had a significantly improved OS in both LM+ (HR = 0.69, p < 0.0001) and LM- (HR = 0.64, p < 0.0001) cohorts. The OS benefit of IO in LM+ cohort remained with propensity score matching analysis (mOS 9.0 vs. 4.4 months, HR = 0.62, p < 0.0001). Further exploratory analysis focusing on those treated with multiagent chemotherapy showed that the addition of IO improved OS in both LM+ (HR = 0.77, p < 0.0001) and LM- (HR = 0.79, p < 0.0001) cohorts. Conclusions: This retrospective study using one of the largest cancer databases suggests that use of IO improves OS of NSCLC patients with LM regardless of chemotherapy status, and its magnitude of OS benefit is similar to that in LM- patients. [Table: see text]
Thoracic SMARCA4-deficient cancer descriptors and clinicopathologic determinants of survival: Analysis of a pooled database.
Authors: Powell Frankie Lee , Haddad Philip A. 
Published: June 2023

9049 Background: Inactivation of SMARCA4, a catalytic subunit of the SWI/SNF complex, has been linked to high-grade aggressive cancers with poor prognoses. SMARCA4-deficient thoracic tumors (SDTT) can involve any part of the chest cavity, including the lungs, mediastinum, pleura, and chest wall. SDTT’s detailed clinical features and optimal treatment still need to be clarified. Therefore, we conducted this pooled database analysis to delineate key clinicopathological characteristics, prognostic indicators, and treatment modalities that affect survival in this unique group of thoracic cancers. Methods: To study the demographic characteristics, molecular and immunohistochemical signatures, therapeutic interventions, survival, and prognostic factors, we compiled a pooled database of 120 cases of SDTT. Kaplan-Meier survival curves were constructed. Cox proportional hazards model and Log-rank tests were used to assess the influence of demographic and clinicopathologic factors on overall survival (OS). Results: A total of 120 patients with confirmed SDTT were identified. The median age was 54, with a peak incidence between 56 and 68. There was a male preponderance with M:F of 3. The median duration of symptoms before diagnosis was 3.5 months. Patients presented with local disease in 11%, locally advanced in 21%, and metastases in 61%. The primary sites were the lungs (45%), mediastinum (42%), and pleura (13%). Common metastatic sites were bone (32%), adrenals (30%), liver (20%), Brain (20%), and lungs (18%). The median OS of the whole group was 6 months. Ninety percent of patients had a smoking history with a median of 26 pack-years. Histology comprised epithelioid/rhabdoid (79%) and carcinoma (adenocarcinoma, mucinous, and undifferentiated, 21%). Carcinomas had a better median OS than sarcomatous histology (11 vs. 6 months, p=0.03). Furthermore, early stages (N0/N1) had a superior median OS compared to advanced stages (N≥2, M+) (16 vs. 5 months, p=0.02). Compared to no treatment, local therapies (surgery (S) or radiation (RT)), combination chemotherapy (CT), and combined modalities (CT±S/RT) were statistically superior with a median OS of 1, 4, 6, and 11 months, respectively (p<0.0001). Further analysis revealed CT+S had superior median OS to CT+RT (16 vs. 9.5 months). Moreover, those with immune checkpoint inhibitors incorporated into their therapies had the best median OS outcomes (p<0.0001). Age, sex, primary site, and size did not impact OS. Conclusions: This study presents updated clinicopathologic data from a pooled cohort of patients with SDTT cancers. It identifies the histologic type, stage, and treatment approach as critical determinants of OS.
Safety, pharmacokinetics (PK), pharmacodynamics (PD) and preliminary efficacy of AZD2936, a bispecific antibody targeting PD-1 and TIGIT, in checkpoint inhibitor (CPI)-experienced advanced/metastatic non-small-cell lung cancer (NSCLC): First report of ARTEMIDE-01.
Authors: Rohrberg Kristoffer Staal , Brandão Mariana , Castanon Alvarez Eduardo , Felip Enriqueta , Gort Eelke Hiddo , Hiltermann T.Jeroen Jeroen Nicolaas , Izumi Hiroki , Kim Dong-Wan , Kim Sang-We , Paz-Ares Luis G. , Solomon Benjamin J. , Steinbusch Laurie , Wauters Els , Yoshida Tatsuya , Chen Huifang , Goldwin Andrew , Jiang Yu , Achour Ikbel , Drachsler Moritz Wolfgang , Cho Byoung Chul 
Published: June 2023

9050 Background: PD-1 and TIGIT are implicated in cancer-related T cell immunosuppression. AZD2936 is a bispecific, humanized IgG1 (triple-mutated to minimize Fc effector function) targeting PD-1 and TIGIT. It has demonstrated encouraging activity compared to both anti-PD-1 and anti-PD-1/-TIGIT combinations in murine models. We report data from dose escalation (Part A) and an expansion cohort (Part B) of the first-in-human study ARTEMIDE-01 (NCT04995523). Methods: This open-label, multicenter study enrolled pts with advanced NSCLC who had prior CPI treatment and a PD-L1 tumor proportion score ≥1%. Part A evaluated doses of 70–1500 mg IV Q3W; Part B evaluated the recommended phase 2 dose (RP2D). Primary endpoints included safety, tolerability, dose-limiting toxicities (DLTs) and preliminary efficacy. Secondary endpoints included PK and PD, defined as percentage PD-1 and TIGIT receptor occupancy (RO). Results: As of Dec 5, 2022, 80 pts were enrolled (Part A, n=48; Part B, n=32). Pts were 62.5% male, median age 63.5 years; 72.5% had adenocarcinoma, 23.8% had squamous cell carcinoma; 96.3% had metastatic disease; and 22.5% had brain metastases. They had a median of 2 prior regimens. Median duration of therapy was 11 wks. AZD2936 was well tolerated with no DLTs. In total, 46.3% of pts had treatment-related adverse events (TRAEs), all grade 1–3; the most common were pruritus, rash and lipase increased (6.3% each). Serious TRAEs occurred in 3 pts (3.8%): immune system disorder, acute hepatitis and fatigue (n=1 each). AZD2936 systemic exposure increased in a near dose-proportional manner. Doses of ≥210 mg achieved ~90% PD-1 and TIGIT RO in peripheral T cells. The RP2D was determined to be 750 mg Q3W based on safety, preliminary efficacy, PK/PD and modeling analysis predicting intratumoral RO. Among 76 evaluable pts, 3 had a partial response and 30 had stable disease (Table). Time to response was 1.9–4.0 mos and duration of response was 2.1–6.4 mos. Conclusions: In this interim analysis, AZD2936 showed an acceptable safety profile and preliminary antitumor activity in pts with advanced/metastatic NSCLC previously treated with standard therapy including CPIs. Further exploration of AZD2936 in CPI-naïve NSCLC pts, including a randomized dose optimization cohort is ongoing. Clinical trial information: NCT04995523 . [Table: see text]
Clinical outcomes among patients with advanced non-small cell lung cancer who received targeted therapy in a real-world setting.
Authors: Yang Mo , MacEwan Joanna P. , Sriteja Boppudi Sai , McClain Monica , O'Hara Richard , Liu Frank , Paik Paul K. 
Published: June 2023

9051 Background: In the past decade, therapies targeting EGFR, KRAS, ALK, ROS1, BRAF, NTRK, MET, RET, HER2 and PD-L1 were approved and recommended by National Comprehensive Cancer Network (NCCN) for use in advanced non-small cell lung cancer (aNSCLC). This study compared real-world clinical outcomes in biomarker positive patients with aNSCLC who received treatments based on the NCCN NSCLC Guidelines (v5.2021) versus other therapies in the US. Methods: This is a retrospective cohort study of patients with aNSCLC using the TEMPUS oncology dataset. Patients were included if they were diagnosed with stage IIIB-IV NSCLC (index date) between 1/1/2012 and 12/31/2020, ≥18 years of age at index, were biomarker (i.e., EGFR, KRAS, ALK, ROS1, BRAF, NTRK, MET, RET, or PD-L1) positive, and received at least one line of treatment. Patients were stratified by NCCN recommended treatment (v5.2021) receipt anytime following aNSCLC diagnosis. Median overall survival (mOS), progression free survival (mPFS), and time to next treatment (mTTNT) were evaluated by treatment group using Kaplan Meier analysis. Patient demographic and clinical characteristics were evaluated as potential predictors of receipt of NCCN recommended therapy. Results: Of the 2,158 biomarker positive patients who met study criteria, 55.7% (N=1,201) received NCCN recommended treatment. PDL1 (38.0%), EGFR (32.2%), and/or KRAS (30.3%) were the most common over-expressions/mutations. Biomarker positive patients with aNSCLC treated with NCCN recommended treatment (N=1,201) in any line had significantly longer mOS (24.7mo, 95% CI: 22.5–27.6) than those treated with non-recommended treatment (N=957, 19.8mo, 95% CI: 17.5–22.6) (p<0.001). Biomarker positive patients with aNSCLC treated with NCCN recommended treatment also had significantly longer mPFS (8.5mo, 95% CI: 7.9–9.0) and mTTNT (20.6mo, 95% CI:19.3–23.7) than those treated with non-recommended treatment (4.9mo, 95% CI: 4.5–5.4) and (11.0mo, 95% CI: 10.0–12.7), respectively (both p<0.001). Never smokers (vs current smokers), patients of unknown or other race (vs whites), and patients who received 2 or more lines of treatment (vs 1) were more likely to receive NCCN recommended treatment and those with squamous or other/unknown histology (vs non-squamous) or missing ECOG scores (vs ECOG 0) were less likely to receive NCCN recommended treatment. Conclusions: In this study, biomarker positive patients with aNSCLC who received NCCN recommended treatment had significantly longer mOS, mPFS, and mTTNT than those who were treated with non-recommended regimens. Following the recommendations of the NCCN NSCLC Panel improves real-world clinical outcomes among biomarker positive patients with aNSCLC. Meanwhile, some biomarker positive patients—including current smokers and those with squamous cell histology—were less likely to receive targeted treatments.
Long-term outcomes of tepotinib in patients with MET exon 14 skipping NSCLC from the VISION study.
Authors: Paik Paul K. , Garassino Marina Chiara , Le Xiuning , Thomas Michael , Sakai Hiroshi , Veillon Remi , Smit Egbert F. , Mazieres Julien , Cortot Alexis B , Raskin Jo , Viteri Santiago , Yang James Chih-Hsin , Ahn Myung-Ju , Wu Yi-Long , Zhao Jun , Adrian Svenja , Berghoff Karin , Bruns Rolf , Johne Andreas , Felip Enriqueta 
Published: June 2023

9060 Background: Tepotinib is a highly selective MET inhibitor with clinical activity in patients (pts) with MET exon 14 ( METex14) skipping NSCLC. We previously reported robust and durable activity of tepotinib from the Phase II VISION study (NCT02864992; data cut: Feb 20, 2022; median follow-up: 26.1 months [mos]; Thomas, et al. WCLC 2022). Here, we report long-term outcomes from VISION, fulfilling an FDA post-market requirement (data cut: Nov 20, 2022; follow-up: Cohort A [primary cohort] ≥35 mos, Cohort C [confirmatory cohort] ≥18 mos). Methods: Pts with advanced METex14 skipping NSCLC detected by liquid and/or tissue (T+) biopsy received tepotinib 500 mg (450 mg active moiety) once daily. The primary endpoint was objective response by independent review using RECIST v1.1. Secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety. Results: Of 313 pts enrolled, median age was 72 years (range 41–94) and pts received tepotinib for a mean (standard deviation [SD]) of 11.5 mos (11.6); median follow-up was 32.6 mos (range 0.3–71.9). First line (1L) pts (n=164; median age: 74 years [range 47–94]; male: 50.6%; ECOG PS 1: 72.0%; smoking history: 53.7%) received tepotinib for a mean (SD) of 12.4 mos (12.2), with 27 pts still receiving treatment. ORR was 57.3% (95% CI: 49.4, 65.0), mDOR was 46.4 mos (13.8, not estimable [ne]), mPFS was 12.6 mos (9.7, 17.7), and mOS was 21.3 mos (14.2, 25.9). Among 111 1L T+ pts, ORR was 58.6% (48.8, 67.8), mDOR was 46.4 mos (15.2, ne), mPFS was 15.9 mos (11.0, 49.7), and mOS was 29.7 mos (18.8, ne) (Table). Second-or-later line (2L+) pts (n=149; median age: 71 years [range 41–89]; male: 47.7%; ECOG PS 1: 75.8%; smoking history: 40.9%) received tepotinib for a mean (SD) of 10.5 mos (11.0), with 10 pts still receiving treatment. ORR was 45.0% (36.8, 53.3) and mDOR was 12.6 mos (9.5, 18.5). Across all 313 pts, ORR was 51.4% (45.8, 57.1), mDOR was 18.0 mos (12.4, 46.4), mPFS was 11.2 mos (9.5, 13.8), and mOS was 19.6 mos (16.2, 22.9). No new safety concerns were observed. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 34.8% of pts; 14.7% of pts discontinued treatment due to TRAEs. Any grade related peripheral edema occurred in 67.1% of pts (Grade ≥3: 11.2%). Conclusions: The long-term outcomes of VISION demonstrate the robust and durable clinical activity of tepotinib, particularly in 1L T+ pts, and manageable safety profile, further defining its use in clinical practice. Clinical trial information: NCT02864992 . [Table: see text]
Management of patients with ALK-positive advanced non-small cell lung cancer who received brain radiotherapy on study in the phase 3 CROWN trial.
Authors: Bauer Todd Michael , Felip Enriqueta , Mok Tony S. K. , Wu Yi-Long , Liu Geoffrey , Goto Yasushi , Kim Dong-Wan , Paolini Jolanda , Polli Anna , Solomon Benjamin J. 
Published: June 2023

9063 Background: Approximately 30% of patients with ALK-positive non-small cell lung cancer (NSCLC) present with brain metastases at diagnosis. Lorlatinib is a potent brain-penetrant ALK tyrosine kinase inhibitor (TKI) that showed improved time to intracranial (IC) progression compared with crizotinib in patients with and without brain metastases at baseline. This post hoc analysis from the phase 3 CROWN study summarizes the management of patients who received brain radiotherapy (RT) during the study. Methods: In the CROWN study, 296 patients with previously untreated ALK-positive advanced NSCLC were randomized 1:1 to receive oral lorlatinib 100 mg once daily (n = 149) or crizotinib 250 mg twice daily (n = 147). Patients who received brain RT while on study treatment or after the initiation of subsequent systemic anticancer therapy were included in this post hoc analysis. Results: As of September 20, 2021, at approximately 3 years of follow-up, median time to IC progression was not reached (NR; 95% CI, NR-NR) in the lorlatinib arm and was 16.6 (95% CI, 11.1-NR) months in the crizotinib arm. At the time of this analysis, 4 of 149 patients (2.7%) in the lorlatinib arm and 20 of 147 patients (13.6%) in the crizotinib arm received brain RT; study treatment was ongoing in 2 of 4 patients (50.0%) in the lorlatinib arm and discontinued in all 20 patients in the crizotinib arm. Median time from randomization to first brain RT was 18.2 (range, 6.4-31.3) months in the lorlatinib arm and 11.1 (range, 2.5-37.5) months in the crizotinib arm. In patients who had brain RT, median duration of treatment was 20.0 (IQR, 6.3-37.1) months with lorlatinib and 7.8 (IQR, 4.0-11.1) months with crizotinib. In the lorlatinib arm, 2 of 4 patients (50.0%) received concomitant brain RT and continued lorlatinib beyond progression. In the crizotinib arm, patients received brain RT while on study treatment or on subsequent systemic anticancer therapies with ALK TKIs or chemotherapy. Follow-up analysis is ongoing. Conclusions: At approximately 3 years of follow-up in the CROWN study, fewer patients in the lorlatinib arm received brain RT than those in the crizotinib arm. At the time of this analysis, study treatment was ongoing in 2 of 4 patients (50.0%) in the lorlatinib arm but was discontinued in all patients in the crizotinib arm. Patients were mostly managed with other ALK TKIs and/or chemotherapy following brain RT in the crizotinib arm. ClinicalTrials.gov: NCT03052608. Clinical trial information: NCT03052608 .