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In recent years, non–small cell lung cancer (NSCLC) entered in a new era of anticancer treatments with the success of checkpoint inhibitors (CPIs). These are now part of daily practice from locally advanced to metastatic NSCLC. However, the registration phase III trials are highly selective and not fully representative of the patients seen in real-world clinical practice. This is particularly obvious for older and frail patients, which represent the majority of NSCLC cases worldwide. The median age of the patients enrolled in clinical trials is 10 years younger than what is seen in clinic and patients with performance status (PS) ≥2 were excluded from registration studies. No strong conclusions can be drawn from the available trials where older and frail patients have been excluded. The majority of data on efficacy according to age are derived from underpowered subgroup analysis and there are no age-specific safety data published. Current data suggest that older patients may derive a similar benefit with no increased toxicity when compared with younger patients. However, the recent development of immunotherapychemotherapy combinations and the potential higher incidence of toxicity, raise additional concerns for these populations where adequate patient selection is paramount. CPI is not recommended for patients with PS 3–4 and should be considered with caution for those with PS 2. The evidence for patients with pre-existing autoimmune disease (AID), organ transplant or chronic viral infections (such us viral hepatitis B and C or human immunodeficiency virus) is less clear and low level. Although CPI are potentially safe in selected patients with AID with minimal activity and well-controlled chronic viral infections, patients with solid organ transplant face a significant risk of graft loss and death. Therefore, a decision to treat these groups of patients should always be discussed at a multidisciplinary level. • Checkpoint inhibitors revolutionised the treatment pathway for advanced non–small cell lung cancer (NSCLC). • There is increasing evidence supporting their use in older cancer patients. • Data on patients with a performance status score of 2 raise concerns on its efficacy within NSCLC. • Data is scarce for patients with autoimmune disease, organ transplant, or chronic viral infections. [ABSTRACT FROM AUTHOR]

Background: Burnout in health care professionals could have serious negative consequences on quality of patient care, professional satisfaction and personal life. Our aim was to investigate the burnout prevalence, work and lifestyle factors potentially affecting burnout amongst European oncologists⩽40 (YOs). Methods: A survey was conducted using the validated Maslach Burnout Inventory (MBI) and additional questions exploring work/lifestyle factors. Statistical analyses were carried out to identify factors associated with burnout. Results: Total of 737 surveys (all ages) were collected from 41 European countries. Countries were divided into six regions. Results from 595 (81%) YOs were included (81% medical oncologists; 52% trainees, 62% women). Seventy-one percent of YOs showed evidence of burnout (burnout subdomains: depersonalization 50%; emotional exhaustion 45; low accomplishment 35%). Twenty-two percent requested support for burnout during training and 74% reported no hospital access to support services. Burnout rates were significantly different across Europe (P<0.0001). Burnout was highest in central European (84%) and lowest in Northern Europe (52%). Depersonalization scores were higher in men compared with women (60% versus 45% P=0.0001) and low accomplishment was highest in the 26-30 age group (P<0.01). In multivariable linear regression analyses, European region, work/life balance, access to support services, living alone and inadequate vacation time remained independent burnout factors (P<0.05). Conclusions: This is the largest burnout survey in European Young Oncologists. Burnout is common amongst YOs and rates vary across Europe. Achieving a good work/life balance, access to support services and adequate vacation time may reduce burnout levels. Raising awareness, support and interventional research are needed. [ABSTRACT FROM AUTHOR]

In recent years, methods that allow for an objective evaluation of perceived comfort, in terms of postural, physiological, cognitive and environmental comfort, have received a great deal of attention from researchers. This paper focuses on one of the factors that influences physiological comfort perception: the temperature difference between users and the objects with which they interact. The first aim is to create a measuring system that does not affect the perceived comfort during the temperatures' acquisition. The main aim is to evaluate how the temperature at the human-mattress interface can affect the level of perceived comfort. A foam mattress has been used for testing in order to take into account the entire back part of the human body. The temperature at the interface was registered by fourteen 100 Ohm Platinum RTDs (Resistance Temperature Detectors) placed on the mattress under the trunk, the shoulders, the buttocks, the legs, the thighs, the arms and the forearms of the test subject. 29 subjects participated in a comfort test in a humidity controlled environment. The test protocol involved: dress-code, anthropometric-based positioning on mattress, environment temperature measuring and an acclimatization time before the test. At the end of each test, each of the test subject's thermal sensations and the level of comfort perception were evaluated using the ASHRAE (American Society of Heating, Refrigerating and Air-Conditioning Engineers) scale. The data analyses concerned, in the first instance, correlations between the temperature at the interface and comfort levels of the different parts of the body. Then the same analyses were performed independently of the body parts being considered. The results demonstrated that there was no strong correlation among the studied variables and that the total increase of temperature at interface is associated with a reduction in comfort. [ABSTRACT FROM AUTHOR]

Abstract: Background: Early stage Non-Small Cell Lung Cancer (NSCLC) is potentially curable with surgery. ESMO guidelines recommend cisplatin-based adjuvant chemotherapy (CT) for completely resected stage II–III NSCLC. There is limited evidence for the use of adjuvant CT and/or radiotherapy (RT) in incompletely resected (R1) early stage NSCLC. Materials and methods: A European survey of thoracic oncologists was conducted to evaluate use of adjuvant CT and RT for R1-resected NSCLC and to identify factors influencing treatment decisions. Demographics and information on clinical stage, regimens, cycles planned, radiotherapy sites, multidisciplinary management and discussion about inconclusive evidence with the patient were collected. Univariate and multivariate analyses were performed. Results: 768 surveys were collected from 41 European countries. 82.9% of participants were medical oncologists; 49.3% ESMO members; 37.1% based in University Hospitals; 32.6% practicing oncology for over 15 years and 81.4% active in research. 91.4% of participants prescribed adjuvant CT and mostly cisplatin/vinorelbine (81.2%) or cisplatin/gemcitabine (42.9%). 85% discussed limited clinical evidence with the patient. In the univariate analysis, a statistically significant association with CT prescription was found for medical oncology specialty (p <0.001), ESMO membership (p <0.001), activity in clinical research (p =0.002) and increased frequency of ESMO guidelines consultation (p for trend <0.001). 48.3% of participants prescribed adjuvant RT and its prescription were associated with radiation oncology specialty (p <0.001), not being an ESMO member (p <0.001), years practicing specialty (p for trend=0.001), workload of lung cancer patients (p for trend=0.027) and decreased frequency in consulting ESMO guidelines (p <0.001). In the multivariate analysis, medical oncology and radiation oncology were the best discriminator for prescription of adjuvant CT and RT, respectively. Conclusion: This survey demonstrates that adjuvant CT and RT are commonly used in clinical practice for R1-resected NSCLC despite limited evidence. Prospective trials are necessary to clarify optimal management in this setting. [Copyright &y& Elsevier]

Amivantamab-lazertinib significantly prolonged progression-free survival (PFS) versus osimertinib in patients with epidermal growth factor receptor (EGFR)-mutant advanced non-small-cell lung cancer [NSCLC; hazard ratio (HR) 0.70; P < 0.001], including those with a history of brain metastases (HR 0.69). Patients with TP53 co-mutations, detectable circulating tumor DNA (ctDNA), baseline liver metastases, and those without ctDNA clearance on treatment have poor prognoses. We evaluated outcomes in these high-risk subgroups. This analysis included patients with treatment-naive, EGFR -mutant advanced NSCLC randomized to amivantamab-lazertinib (n = 429) or osimertinib (n = 429) in MARIPOSA. Pathogenic alterations were identified by next-generation sequencing (NGS) of baseline blood ctDNA with Guardant360 CDx. Ex19del and L858R ctDNA in blood was analyzed at baseline and cycle 3 day 1 (C3D1) with Biodesix droplet digital polymerase chain reaction (ddPCR). Baseline ctDNA for NGS of pathogenic alterations was available for 636 patients (amivantamab-lazertinib, n = 320; osimertinib, n = 316). Amivantamab-lazertinib improved median PFS (mPFS) versus osimertinib for patients with TP53 co-mutations {18.2 versus 12.9 months; HR 0.65 [95% confidence interval (CI) 0.48-0.87]; P = 0.003} and for patients with wild-type TP53 [22.1 versus 19.9 months; HR 0.75 (95% CI 0.52-1.07)]. In patients with EGFR -mutant, ddPCR-detectable baseline ctDNA, amivantamab-lazertinib significantly prolonged mPFS versus osimertinib [20.3 versus 14.8 months; HR 0.68 (95% CI 0.53-0.86); P = 0.002]. Amivantamab-lazertinib significantly improved mPFS versus osimertinib in patients without ctDNA clearance at C3D1 [16.5 versus 9.1 months; HR 0.49 (95% CI 0.27-0.87); P = 0.015] and with clearance [24.0 versus 16.5 months; HR 0.64 (95% CI 0.48-0.87); P = 0.004]. Amivantamab-lazertinib significantly prolonged mPFS versus osimertinib among randomized patients with [18.2 versus 11.0 months; HR 0.58 (95% CI 0.37-0.91); P = 0.017] and without baseline liver metastases [24.0 versus 18.3 months; HR 0.74 (95% CI 0.60-0.91); P = 0.004]. Amivantamab-lazertinib effectively overcomes the effect of high-risk features and represents a promising new standard of care for patients with EGFR- mutant advanced NSCLC. [Display omitted] • Amivantamab-lazertinib significantly improved PFS in patients with detectable ctDNA at baseline versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients without ctDNA clearance at C3D1 versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients with TP53 co-mutations versus osimertinib. • Amivantamab-lazertinib significantly improved PFS in patients with liver metastases versus osimertinib. • Eighty-nine percent of patients with analyzable ctDNA by NGS from MARIPOSA had at least one high-risk baseline feature. [ABSTRACT FROM AUTHOR]

Amivantamab plus carboplatin–pemetrexed (chemotherapy) with and without lazertinib demonstrated antitumor activity in patients with refractory epidermal growth factor receptor (EGFR)-mutated advanced non-small-cell lung cancer (NSCLC) in phase I studies. These combinations were evaluated in a global phase III trial. A total of 657 patients with EGFR -mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomized 2 : 2 : 1 to receive amivantamab–lazertinib–chemotherapy, chemotherapy, or amivantamab–chemotherapy. The dual primary endpoints were progression-free survival (PFS) of amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy. During the study, hematologic toxicities observed in the amivantamab–lazertinib–chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion. All baseline characteristics were well balanced across the three arms, including by history of brain metastases and prior brain radiation. PFS was significantly longer for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy [hazard ratio (HR) for disease progression or death 0.48 and 0.44, respectively; P < 0.001 for both; median of 6.3 and 8.3 versus 4.2 months, respectively]. Consistent PFS results were seen by investigator assessment (HR for disease progression or death 0.41 and 0.38 for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy, respectively; P < 0.001 for both; median of 8.2 and 8.3 versus 4.2 months, respectively). Objective response rate was significantly higher for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy (64% and 63% versus 36%, respectively; P < 0.001 for both). Median intracranial PFS was 12.5 and 12.8 versus 8.3 months for amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy (HR for intracranial disease progression or death 0.55 and 0.58, respectively). Predominant adverse events (AEs) in the amivantamab-containing regimens were hematologic, EGFR- , and MET -related toxicities. Amivantamab–chemotherapy had lower rates of hematologic AEs than amivantamab–lazertinib–chemotherapy. Amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib. Longer follow-up is needed for the modified amivantamab–lazertinib–chemotherapy regimen. [Display omitted] • Amivantamab–chemotherapy improved PFS and intracranial PFS versus chemotherapy. • Amivantamab–lazertinib–chemotherapy improved PFS and intracranial PFS versus chemotherapy. • Predominant AEs in the amivantamab-containing arms were hematologic, EGFR , and MET related. • MARIPOSA-2 is the first study to demonstrate improved PFS versus chemotherapy after disease progression on osimertinib. [ABSTRACT FROM AUTHOR]

Purpose/objective(s): Concurrent chemoradiotherapy (CCRT) with etoposide and platinum (carboplatin/cisplatin) plus the anti‒PD-1 antibody pembrolizumab (pembro) has shown antitumor activity and acceptable safety in patients (pts) with limited-stage small-cell lung cancer (LS-SCLC). The poly (ADP-ribose) polymerase (PARP) inhibitor, olaparib, has shown activity in combination with checkpoint inhibitors in SCLC. KEYLYNK-013 (NCT04624204) is a randomized, placebo-controlled, double-blind phase 3 trial of pembro plus CCRT followed by pembro with or without olaparib in pts with newly diagnosed LS-SCLC.Materials/methods: Eligible pts are those aged ≥18 years with previously untreated LS-SCLC, ECOG PS 0/1, and adequate pulmonary function. Pts are randomized 1:1:1 to receive pembro 200 mg Q3W (groups A and B) or pembro placebo (saline) Q3W (group C) during the chemoradiation phase. All pts also receive 4 cycles of chemotherapy (etoposide 100 mg/m2 on days 1, 2, and 3 of each cycle and investigator's choice of carboplatin AUC 5 mg/mL/min or cisplatin 75 mg/m2 on day 1 of each cycle) with definitive thoracic radiotherapy (total dose of 45 Gy in 30 fractions twice daily over 3 weeks or 66 Gy in 33 fractions once daily over 6.5 weeks starting on day 1 of cycle 2). After chemoradiation, prophylactic cranial irradiation is strongly recommended for pts with CR/PR or at investigator's discretion for pts with SD. Postchemoradiation pts receive pembro 400 mg Q6W plus olaparib placebo (group A), or pembro 400 mg Q6W plus olaparib 300 mg BID (group B), or pembro placebo plus olaparib placebo (group C) for 9 cycles/12 months. Randomization is stratified by ECOG PS (0 vs 1), SCLC stage (I/II vs III), radiation fractionation (twice vs once daily), and region (east Asia vs North America/western Europe/UK/Australia vs rest of world). Tumor imaging occurs at baseline, within 12 weeks of cycle 1 day 1, followed by Q9W to the end of year 2, Q12W in year 3, Q16W in year 4, every 6 months in year 5, and annually thereafter. Imaging is assessed per RECIST v1.1 by blinded independent central review. AEs are made per NCI-CTCAE v5.0. Health-related quality of life is assessed using EORTC-QLQ-C30 and QLQ-LC13. Primary endpoints are OS and PFS per RECIST v1.1 by blinded independent central review. OS and PFS are estimated by the Kaplan-Meier method. Between-group differences will be evaluated with stratified log-rank tests and Cox proportional hazard models with Efron's method of tie handling. Secondary endpoints include ORR, duration of response, safety, and pt-reported outcomes. Enrollment began in Dec 2020 and is ongoing at 43 sites in 11 countries as of Feb 24, 2021.Results: TBD CONCLUSION: TBD. [ABSTRACT FROM AUTHOR]

The number of cancer patients in Europe is rising and significant advances in basic and applied cancer research are making the provision of optimal care more challenging. The concept of cancer as a systemic, highly heterogeneous and complex disease has increased the awareness that quality cancer care should be provided by a multidisciplinary team (MDT) of highly qualified healthcare professionals. Cancer patients also have the right to benefit from medical progress by receiving optimal treatment from adequately trained and highly skilled medical professionals. Built on the highest standards of professional training and continuing medical education, medical oncology is recognised as an independent medical specialty in many European countries. Medical oncology is a core member of the MDT and offers cancer patients a comprehensive and systemic approach to treatment and care, while ensuring evidence-based, safe and cost-effective use of cancer drugs and preserving the quality of life of cancer patients through the entire ‘cancer journey’. Medical oncologists are also engaged in clinical and translational research to promote innovation and new therapies and they contribute to cancer diagnosis, prevention and research, making a difference for patients in a dynamic, stimulating professional environment. Medical oncologists play an important role in shaping the future of healthcare through innovation and are also actively involved at the political level to ensure a maximum contribution of the profession to Society and to tackle future challenges. This position paper summarises the multifarious and vital contributions of medical oncology and medical oncologists to today's and tomorrow's professional cancer care. [ABSTRACT FROM AUTHOR]

• In asymptomatic patients, chemotherapy alone was the most commonly recommended 1st line treatment. • For symptomatic patients, WBRT was the most common 1st line treatment. • Significant variation in decision-making exists among European SCLC experts. Brain metastases (BM) are common in patients with small cell lung cancer (SCLC). In recent years, the role of whole brain radiotherapy (WBRT) for brain metastases in lung cancer is being reevaluated, especially in the context of new systemic treatments available for SCLC. With this analysis, we investigate decision-making in SCLC patients with BM among European experts in medical oncology and radiation oncology. We analyzed decision-making from 13 medical oncologists (selected by IASLC) and 13 radiation oncologists (selected by ESTRO) specialized in SCLC. Management strategies of individual experts were converted into decision trees and analyzed for consensus. In asymptomatic patients, chemotherapy alone is the most commonly recommended first line treatment. In asymptomatic patients with limited volume of brain metastases, a higher preference for chemotherapy without WBRT among medical oncologists compared to radiation oncologists was observed. For symptomatic patients, WBRT followed by chemotherapy was recommended most commonly. For limited extent of BM in symptomatic patients, some experts chose stereotactic radiotherapy as an alternative to WBRT. Significant variation in clinical decision-making was observed among European SCLC experts for the first line treatment of patients with SCLC and BM. [ABSTRACT FROM AUTHOR]

• Second-line therapy of stage IV SCLC is heterogeneous among European experts. • After 6 months from first-line treatment, 92 % recommend platinum re-challenge. • 3–6 months after first-line treatment no consensus was found. • In very early recurrence CAV for fit & topotecan for unfit patients was recommended. Stage IV small cell lung cancer (SCLC) is associated with short survival and progression after first-line systemic therapy frequently occurs within months. Although topotecan is approved for second-line treatment, its efficacy is limited, and treatment heterogeneity exists. The decision-making patterns for second line treatment of 13 European medical oncologists with expertise in SCLC were analyzed. The two criteria most relevant to decision-making were the performance status and the interval of recurrence since first-line treatment. With an interval of less than 3 months since the end of first-line chemotherapy, 62 % of the experts recommended cyclophosphamide, doxorubicin and vincristine (CAV) for fit patients and 54 % recommended topotecan for unfit patients. For an interval of more than 6 months, a clear consensus for a re-challenge with a platinum doublet was achieved (92 %). However, there was no consensus on the second-line therapy with an interval of 3–6 months since the end of first-line therapy. Real world practice may differ from recommendations in general guidelines and cannot always be directly derived from trial results as other factor such as habits, patient's preference, convenience or costs have to be factored in. [ABSTRACT FROM AUTHOR]

The addition of atezolizumab to carboplatin and etoposide (CP/ET) significantly improved progression-free and overall survival for patients with extensive-stage small-cell lung cancer (ES-SCLC) in the IMpower133 study (NCT02763579). We have evaluated adverse events (AEs) and patient-reported outcomes in IMpower133 to assess the benefit–risk profile of this regimen. Patients received four 21-day cycles of CP/ET plus intravenous atezolizumab 1200 mg or placebo (induction phase), followed by atezolizumab or placebo (maintenance phase) until progression or loss of benefit. AEs were assessed and patient-reported outcomes were evaluated every 3 weeks during treatment using the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire – Core 30 (QLQ-C30) and QLQ-LC13. Overall, 394 patients were assessable for safety in the induction phase and 318 in the maintenance phase. The frequency of AEs, grade 3–4 AEs, and serious AEs was similar between arms in both phases. Immune-related AEs were more frequent in the atezolizumab arm during both induction (28% versus 17%; leading to atezolizumab/placebo interruption 9% versus 5%, leading to withdrawal 4% versus 0%) and maintenance (26% versus 15%; leading to atezolizumab/placebo interruption, 3% versus 2%, leading to withdrawal 1% versus 1%), most commonly rash (induction 11% versus 9%, maintenance 14% versus 4%), and hypothyroidism (induction 4.0% versus 0%, maintenance 10% versus 1%). Changes in patient-reported treatment-related symptoms commonly associated with quality of life impairment were generally similar during induction and most of the maintenance phase. Patient-reported function and health-related quality of life (HRQoL) improved in both arms after initiating treatment, with more pronounced and persistent HRQoL improvements in the atezolizumab arm. In patients with ES-SCLC, atezolizumab plus CP/ET has a comparable safety profile to placebo plus CP/ET, and the addition of atezolizumab did not adversely impact patient-reported HRQoL. These data demonstrate the positive benefit–risk profile of first-line atezolizumab plus CP/ET in ES-SCLC and further support this regimen as a new standard of care in this setting. NCT02763579. • First-line atezolizumab plus CP/ET had a similar safety profile to placebo plus CP/ET in both induction and maintenance. • The addition of atezolizumab did not adversely impact patient-reported health-related quality of life. • The risk:benefit ratio further supports atezolizumab plus CP/ET as a new standard of care in ES-SCLC. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Afatinib prolongs progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who were previously sensitive to erlotinib or gefitinib. This study investigated experience of afatinib under a Named Patient Use (NPU) programme. Patients and methods: Retrospective data for 63 patients were collected, including demographics, dose, toxicity and clinical efficacy. Results: Response rate and median PFS were 14.3% and 2.6months, respectively. Diarrhoea and rash were the most common toxicities; 46% of patients required a dose reduction and 41% had a dose delay. Conclusions: Efficacy and safety in the NPU programme are consistent with the LUX-Lung 1 trial. [Copyright &y& Elsevier]

Abstract: Introduction: Afatinib prolongs progression-free survival (PFS) in patients with non-small cell lung cancer (NSCLC) who were previously sensitive to erlotinib or gefitinib. This study investigated experience of afatinib under a Named Patient Use (NPU) programme. Patients and methods: Retrospective data for 63 patients were collected, including demographics, dose, toxicity and clinical efficacy. Results: Response rate and median PFS were 14.3% and 2.6months, respectively. Diarrhoea and rash were the most common toxicities; 46% of patients required a dose reduction and 41% had a dose delay. Conclusions: Efficacy and safety in the NPU programme are consistent with the LUX-Lung 1 trial. [ABSTRACT FROM AUTHOR]

Background In the first preplanned interim analysis (IA) from ALTA-1L (NCT02737501; median follow-up BRG/CRZ: 11.0/9.3 mo, 99 PFS events), BRG demonstrated superior BIRC-assessed PFS and improved patient-reported quality of life vs CRZ. We report results of the second IA planned at 75% of 198 expected events. Methods Patients (pts) with ALK inhibitor–naive advanced ALK+ NSCLC and ECOG PS 0–2 were enrolled. One prior chemotherapy for advanced NSCLC was allowed. Asymptomatic CNS metastases were allowed. Pts were stratified by baseline (BL) brain metastases and prior chemotherapy. All pts had brain MRI at each tumor assessment. Pts were randomized 1:1 to BRG 180 mg QD (with 7-day lead-in at 90 mg) or CRZ 250 mg BID. Pts in the CRZ arm were offered BRG at progression. Primary endpoint: BIRC-assessed PFS (RECIST v1.1). Secondary endpoints included confirmed ORR, confirmed iORR, iPFS by BIRC, OS, and safety. Results 275 pts were randomized (BRG/CRZ, n = 137/138); median age 58/60 y. 26%/27% received prior chemotherapy; 29%/30% had BL brain metastases. As of 28 Jun 2019, median follow-up was BRG/CRZ: 24.9/15.2 mo, with 150 PFS events. HR of BIRC-assessed PFS was 0.49 (95% CI 0.35–0.68, log-rank P < 0.0001); BRG mPFS was 24.0 mo (95% CI 18.5–NE) vs CRZ 11.0 mo (95% CI 9.2–12.9). Investigator-assessed PFS HR was 0.43 (95% CI 0.31–0.61, median 29.4 vs 9.2 mo). OS was immature (total events: 33/37, BRG/CRZ). In pts with BL brain metastases, the PFS HR was 0.25. Data were less mature in pts without BL brain metastases treated with BRG. Table shows additional efficacy data. Most common TEAEs grade ≥3: BRG: increased CPK (24.3%) and lipase (14.0%), hypertension (11.8%); CRZ: increased ALT (10.2%), AST (6.6%), and lipase (6.6%). Any grade ILD/pneumonitis (BRG/CRZ): 5.1%/2.2%; discontinuations due to AE (BRG/CRZ): 12.5%/8.8%. Table: LBA1 BIRC-Assessed Efficacy  BRG  CRZ  P Value  All pts (ITT), n  137  138    ORR a , %  79 (71–85 b)  75 (67–82 b)  0.4376 c   Confirmed ORR, %  74 (66–81 b)  62 (53–70 b)  0.0342 c   mDoR d , mo  NE (19–NE b)  14 (9–21 b)    PFS events, n (%)  63 (46)  87 (63)    mPFS, mo  24.0 (18.5–NE b)  11.0 (9.2–12.9 b)    PFS HR  0.49 (0.35–0.68 b)  <0.0001 e   Any BL brain metastases, n  40 f   41 f     PFS events, n (%)  20 (50)  30 (73)    PFS HR  0.25 (0.14–0.46 b)  <0.0001 e     47 g   49 g     iPFS events, n (%)  21 (45)  32 (65)    iPFS HR  0.31 (0.17–0.56 b)  <0.0001 e   No BL brain metastases f , n  97  97    PFS events, n (%)  43 (44)  57 (59)    PFS HR  0.65 (0.44–0.97 b)  0.0298 e   BL measurable brain metastases, n  18  23    iORR a , %  78 (52–94 b)  30 (13–53 b)  0.0036 c   Confirmed iORR, %  78 (52–94 b)  26 (10–48 b)  0.0014 c   Median iDoR d , mo  NE (6–NE b)  9 (4–9 b)    BIRC-Assessed Efficacy  BRG  CRZ  P Value  All pts (ITT), n  137  138    ORR a , %  79 (71–85 b)  75 (67–82 b)  0.4376 c   Confirmed ORR, %  74 (66–81 b)  62 (53–70 b)  0.0342 c   mDoR d , mo  NE (19–NE b)  14 (9–21 b)    PFS events, n (%)  63 (46)  87 (63)    mPFS, mo  24.0 (18.5–NE b)  11.0 (9.2–12.9 b)    PFS HR  0.49 (0.35–0.68 b)  <0.0001 e   Any BL brain metastases, n  40 f   41 f     PFS events, n (%)  20 (50)  30 (73)    PFS HR  0.25 (0.14–0.46 b)  <0.0001 e     47 g   49 g     iPFS events, n (%)  21 (45)  32 (65)    iPFS HR  0.31 (0.17–0.56 b)  <0.0001 e   No BL brain metastases f , n  97  97    PFS events, n (%)  43 (44)  57 (59)    PFS HR  0.65 (0.44–0.97 b)  0.0298 e   BL measurable brain metastases, n  18  23    iORR a , %  78 (52–94 b)  30 (13–53 b)  0.0036 c   Confirmed iORR, %  78 (52–94 b)  26 (10–48 b)  0.0014 c   Median iDoR d , mo  NE (6–NE b)  9 (4–9 b)    BIRC, blinded independent review committee; DoR, duration of response; iDoR, intracranial DoR; iORR, intracranial ORR; iPFS, intracranial PFS; ITT, intent-to-treat; mDoR, median DoR; NE, not estimable; ORR, objective response rate; PFS, progression-free survival. a Response, ≥1 assessment; b 95% CI; c Cochran-Mantel-Haenszel test; d Confirmed responders; e Log-rank; f Per investigator assessment; g Per BIRC assessment. Table: LBA1 BIRC-Assessed Efficacy  BRG  CRZ  P Value  All pts (ITT), n  137  138    ORR a , %  79 (71–85 b)  75 (67–82 b)  0.4376 c   Confirmed ORR, %  74 (66–81 b)  62 (53–70 b)  0.0342 c   mDoR d , mo  NE (19–NE b)  14 (9–21 b)    PFS events, n (%)  63 (46)  87 (63)    mPFS, mo  24.0 (18.5–NE b)  11.0 (9.2–12.9 b)    PFS HR  0.49 (0.35–0.68 b)  <0.0001 e   Any BL brain metastases, n  40 f   41 f     PFS events, n (%)  20 (50)  30 (73)    PFS HR  0.25 (0.14–0.46 b)  <0.0001 e     47 g   49 g     iPFS events, n (%)  21 (45)  32 (65)    iPFS HR  0.31 (0.17–0.56 b)  <0.0001 e   No BL brain metastases f , n  97  97    PFS events, n (%)  43 (44)  57 (59)    PFS HR  0.65 (0.44–0.97 b)  0.0298 e   BL measurable brain metastases, n  18  23    iORR a , %  78 (52–94 b)  30 (13–53 b)  0.0036 c   Confirmed iORR, %  78 (52–94 b)  26 (10–48 b)  0.0014 c   Median iDoR d , mo  NE (6–NE b)  9 (4–9 b)    BIRC-Assessed Efficacy  BRG  CRZ  P Value  All pts (ITT), n  137  138    ORR a , %  79 (71–85 b)  75 (67–82 b)  0.4376 c   Confirmed ORR, %  74 (66–81 b)  62 (53–70 b)  0.0342 c   mDoR d , mo  NE (19–NE b)  14 (9–21 b)    PFS events, n (%)  63 (46)  87 (63)    mPFS, mo  24.0 (18.5–NE b)  11.0 (9.2–12.9 b)    PFS HR  0.49 (0.35–0.68 b)  <0.0001 e   Any BL brain metastases, n  40 f   41 f     PFS events, n (%)  20 (50)  30 (73)    PFS HR  0.25 (0.14–0.46 b)  <0.0001 e     47 g   49 g     iPFS events, n (%)  21 (45)  32 (65)    iPFS HR  0.31 (0.17–0.56 b)  <0.0001 e   No BL brain metastases f , n  97  97    PFS events, n (%)  43 (44)  57 (59)    PFS HR  0.65 (0.44–0.97 b)  0.0298 e   BL measurable brain metastases, n  18  23    iORR a , %  78 (52–94 b)  30 (13–53 b)  0.0036 c   Confirmed iORR, %  78 (52–94 b)  26 (10–48 b)  0.0014 c   Median iDoR d , mo  NE (6–NE b)  9 (4–9 b)    BIRC, blinded independent review committee; DoR, duration of response; iDoR, intracranial DoR; iORR, intracranial ORR; iPFS, intracranial PFS; ITT, intent-to-treat; mDoR, median DoR; NE, not estimable; ORR, objective response rate; PFS, progression-free survival. a Response, ≥1 assessment; b 95% CI; c Cochran-Mantel-Haenszel test; d Confirmed responders; e Log-rank; f Per investigator assessment; g Per BIRC assessment. Conclusions BRG showed durable PFS superiority vs CRZ in ALK inhibitor–naive ALK+ NSCLC. Clinical trial identification NCT02737501. Editorial acknowledgement Peloton Advantage, LLC, an OPEN Health company, Parsippany, NJ, USA, and funded by Millennium Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited, Cambridge, MA, USA. Legal entity responsible for the study ARIAD Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Funding ARIAD Pharmaceuticals, Inc. a wholly owned subsidiary of Takeda Pharmaceutical Company Limited. Disclosure R. Camidge: Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (self): Takeda; Honoraria (self): Arrys/Kyn; Honoraria (self): Novartis; Honoraria (self): Celgene; Honoraria (self): Clovis; Honoraria (self): Orion; Honoraria (self): Revolution Med; Honoraria (self): Lycera; Honoraria (self): Bio-Thera DSMB; Honoraria (self): Hansoh SRC; Honoraria (self): Daichi Sankyo; Honoraria (self): Ignyta; Honoraria (self): Roche/Genentech; Honoraria (self): Mersana Therapeutics; Honoraria (self): G1 Therapeutics; Honoraria (self): Genoptix. H.R. Kim: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. M. Ahn: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Novartis. J.C. Yang: Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Bayer; Honoraria (self), Advisory / Consultancy: Roche/Genentech/Chugai; Honoraria (self), Advisory / Consultancy: Astellas; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Merck Serono; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Novartis; Honoraria (self), Advisory / Consultancy: Celgene; Honoraria (self), Advisory / Consultancy: Merrimack; Honoraria (self), Advisory / Consultancy: Yuhan Pharmaceuticals; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Ono Pharmaceutical; Honoraria (self), Advisory / Consultancy: Daiichi Sankyo; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Hansoh Pharmaceuticals. J. Han: Research grant / Funding (self): Roche. M.J. Hochmair: Honoraria (self): AstraZeneca; Honoraria (self): Bristol-Myers Squibb; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Merck Sharp & Dohme; Honoraria (self): Pfizer; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: Takeda; Advisory / Consultancy: Novartis. K.H. Lee: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: Eli Lilly; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim. A. Delmonte: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim. M.R. Garcia Campelo: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Ariad; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim. F. Griesinger: Advisory / Consultancy: Ariad; Advisory / Consultancy: Takeda; Advisory / Consultancy: Roche; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer. E. Felip: Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Boehringer Ingelheim; Advisory / Consultancy: BMS; Advisory / Consultancy: Celgene; Advisory / Consultancy: Eli Lilly; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: MSD; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy: Roche; Advisory / Consultancy: Takeda; Advisory / Consultancy: Merck. R. Califano: Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self), Advisory / Consultancy: BMS; Honoraria (self), Advisory / Consultancy: Roche; Honoraria (self), Advisory / Consultancy: MSD; Honoraria (self), Advisory / Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory / Consultancy: Takeda; Honoraria (self), Advisory / Consultancy: Novartis. A. Spira: Advisory / Consultancy: Ariad; Advisory / Consultancy: AstraZeneca; Advisory / Consultancy: Clovis Oncology; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. S. Gettinger: Advisory / Consultancy, Research grant / Funding (self): Ariad; Advisory / Consultancy, Research grant / Funding (self): BMS; Advisory / Consultancy: Janssen; Research grant / Funding (self): AstraZeneca/MedImmune; Research grant / Funding (self): Boehringer Ingelheim; Research grant / Funding (self): Incyte; Research grant / Funding (self): Pfizer; Research grant / Funding (self): Roche/Genentech. M. Tiseo: Advisory / Consultancy, Speaker Bureau / Expert testimony: AstraZeneca; Advisory / Consultancy, Speaker Bureau / Expert testimony: BMS; Advisory / Consultancy, Speaker Bureau / Expert testimony: Boehringer Ingelheim; Advisory / Consultancy, Speaker Bureau / Expert testimony: Eli Lilly; Advisory / Consultancy, Speaker Bureau / Expert testimony: MSD; Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Advisory / Consultancy, Speaker Bureau / Expert testimony: Otsuka; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pfizer; Advisory / Consultancy, Speaker Bureau / Expert testimony: Pierre Fabre; Advisory / Consultancy, Speaker Bureau / Expert testimony: Roche. Q. Ni: Full / Part-time employment: Takeda. P. Zhang: Full / Part-time employment: Takeda. S. Popat: Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: Boehringer Ingelheim; Research grant / Funding (institution): Epizyme; Advisory / Consultancy, Research grant / Funding (institution), Travel / Accommodation / Expenses: BMS; Research grant / Funding (institution): Clovis Oncology; Honoraria (self), Advisory / Consultancy, Research grant / Funding (institution): Roche; Research grant / Funding (institution): Lilly; Honoraria (self), Research grant / Funding (institution): Takeda; Honoraria (self), Advisory / Consultancy: AstraZeneca; Honoraria (self): Chugai Pharma; Advisory / Consultancy: Novartis; Advisory / Consultancy: Pfizer; Advisory / Consultancy, Travel / Accommodation / Expenses: MSD; Advisory / Consultancy: Guardant Health; Advisory / Consultancy: AbbVie. [ABSTRACT FROM AUTHOR]