Background: COVID-19 has been suggested as a possible trigger of disease flares in patients with rheumatoid arthritis (RA). However, factors associated with disease flares remain unknown. Objectives: This study aimed to identify factors associated with disease flares in patients with RA following COVID-19. Methods: We selected patients with RA from an online e-survey data from the COVID-19 vaccination in autoimmune diseases (COVAD) study. Demographic data, patient-reported outcomes, comorbidities and pharmacologic treatment were extracted from the database. Disease flare-ups were derived from the e-survey database. Factors associated with disease flare-ups were determined by multivariate logistic regression analysis. Results: In total, 1928 patients with RA were extracted from the COVAD database. Younger age (odds ratio (OR): 0.98, 95% CI: 0.96 – 0.99, p<0.001), ethnicity other than Asian, past history of tuberculosis (OR: 3.80, 95% CI: 1.12 – 12.94, p=0.033), treatment with methotrexate (OR: 2.55, 95% CI: 1.56 – 4.17, p<0.001), poor global physical health (OR: 1.07, 95% CI: 1.00 –1.15, p=0.044) and mental health (OR: 0.91, 95% CI: 0.87 –0.95, p<0.001) were independent factors associated disease flares in patients with RA. Table 1 represents factors associated with disease flare in patients with RA after COVID breakthrough infections and Figure 1 represents forest plots of symptoms of disease flare. Conclusion: Our study highlights important socio-demographic, clinical characteristics and mental health to be associated with flares in patients with RA. This finding may help determine relevant strategies to proactively manage RA patients at risk of flares. REFERENCES: NIL. Acknowledgements: Myositis Association, Myositis India, Myositis UK, Myositis Support and Understanding, the Myositis Global Network, Deutsche Gesellschaft für Muskelkranke e.V. (DGM), Dutch and Swedish Myositis patient support groups, Cure JM, Cure IBM, Sjögren’s India Foundation, Patients Engage, Scleroderma India, Lupus UK, Lupus Sweden, Emirates Arthritis Foundation, EULAR PARE, ArLAR research group, AAAA patient group, Myositis Association of Australia, APLAR myositis special interest group, Thai Rheumatism association, PANLAR, AFLAR NRAS, Anti-Synthetase Syndrome support group, and various other patient support groups and organizations. Disclosure of Interests: None declared.Figure 1Forest plots of symptoms of breakthrough infections and disease flare. Table 1Factors associated with disease flare in patients with RA after COVID breakthrough infectionsUnivariateMultivariateOR95% CIP valueOR95% CIP valueAge0.98(0.97-0.99)<0.001**0.98(0.96-0.99)<0.001**Gender FemaleReferenceMale0.76(0.46-1.24)0.268Ethnicity AsianReferenceReferenceCaucasian3.73(2.15-6.47)<0.001**4.33(2.43-7.72)<0.001**African American/ African4.13(2.02-8.46)<0.001**3.64(1.73-7.64)0.001**Hispanic3.45(1.78-6.66)<0.001**3.71(1.88-7.34)<0.001**Native American/Indigenous/Pacific Islander1.50(0.19-12.01)0.7041.52(0.18-12.60)0.697Mixed2.87(1.17-7.02)0.021*2.94(1.18-7.34)0.021*Other2.65(1.16-6.09)0.021*2.83(1.21-6.64)0.017*Comorbidities Asthma1.49(0.99-2.25)0.0571.21(0.78-1.90)0.394Interstitial Lung Disease1.89(0.99-3.58)0.0532.01(1.00-4.04)0.051Tuberculosis3.41(1.06-10.97)0.040*3.80(1.12-12.94)0.033*Medication Glucocorticoid1.98(1.20-3.25)0.007**1.26(0.71-2.23)0.425Methotrexate2.80(1.82-4.31)<0.001**2.55(1.56-4.17)<0.001**Hydroxychloroquine2.90(1.44-5.84)0.003**1.78(0.76-4.18)0.186Anti TNF agents#3.72(1.68-8.24)0.001**2.33(0.94-5.77)0.066JAK inhibitors +4.27(1.27-14.29)0.019*2.93(0.80-10.78)0.106PROMIS global physical health1.07(1.00-1.15)0.044*1.09(1.00-1.18)0.040*PROMIS global mental health0.91(0.87-0.95)<0.001**0.91(0.87-0.95)<0.001**By Logistic regression. *p<0.05, **p<0.01.#infliximab, adalimumab, certolizumab, golimumab, etanercept+tofacitinib, baricitinib, upadacitinib

Background: Idiopathic inflammatory myopathies (IIM) encompass a group of disorders characterized by muscle inflammation, weakness, and varying levels of systemic involvement. These conditions profoundly impact patients’ quality of life (QoL) due to their chronic nature, physical impairments, and accompanying mental health challenges. Recent literature has highlighted the prevalence of comorbidities in IIM, with cardiovascular damage and depression being particularly prominent and significantly influencing on patient’s QoL. Objectives: This study aims to explore the influence of mental health disorders (MHDs) on the QoL of in patients with IIM. Methods: We examined the prevalence of MHDs in IIM adult patients using the COVAD-2 data. Mental Health Multimorbidity (MHM) was defined as the presence of ≥2 MHDs. PROMIS global physical health (PGP), mental health (PMH), fatigue 4a (F4a), and physical function (SF10) were analyzed using descriptive statistics and linear regression. Hierarchical Clustering on Principal Components was performed to delineate the grouping of IIM patients. Results: Of the 10,740 COVAD participants, 1,523 reported a diagnosis of IIM. The IIM cohort included 470 (30.8%) patients with dermatomyositis (DM), 217 (14.2%) with polymyositis (PM), 375 (24.6%) with Inclusion body inclusion myositis (IBM), 103 (6.7%) with antisynthetase syndrome (ASS), 96 (6.3%) with immune-mediated necrotizing myopathy (IMNM), and 239 (15.6%) with overlap myositis (OM), while the remaining patients were considered “unclassified myositis.” The demographics and characteristics of the study cohort are shown in Table 1A. MHD was present in 34% of the IIM patients, predominantly manifesting as anxiety, with no significant difference across subgroups, except for insomnia, which was notably more prevalent in the OM subgroup (P=0.001).No significant differences were found in the distribution of MHM across the subgroups. It was also noted that patients with MHDs exhibited poorer physical function, as evidenced by lower PGP, PGM, and SF10 scores, and higher F4a scores (all P<0.001). Furthermore, the presence of MHM and active disease were significant predictors of all assessed PROMIS domains (all P<0.001). Age and gender were not found to be associated with physical function scores.Three distinct clusters were identified (Table 2A). Cluster 1 appears to be characterized by patients without a significant multimorbidity burden, generally healthier scores, and an older average age. Cluster 2, with the youngest average age, shows adequate health scores and fewer multimorbidities. Cluster 3, with both single and multiple morbidities, exhibits more mental health issues, poorer health scores, and a middle-range average age. In Cluster 1, DM and IBM were the most common subtypes, whereas OM was predominant in Cluster 2. In Cluster 3, the distribution was more varied, but DM and OM were relatively more common than other subtypes. Conclusion: Our study indicates that patients with a multitude of coexisting conditions and MHDs tend to report poorer outcomes in various aspects of health, such as overall physical and mental health, physical functioning, and fatigue, especially in certain demographic with DM or OM. Recognizing the complex needs of these patients, our findings suggest a need for tailored care approaches. These may encompass specialized medical services or prioritized follow-up strategies to minimize treatment delays. Additionally, we must be cognizant of the increased demand these patients may place on healthcare resources. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests: Maria Rosa Pellico: None declared, Marco Fornaro: None declared, Vincenzo Venerito: None declared, Jessica Day: None declared, Ashima Makol: None declared, Parikshit Sen: None declared, Esha Kadam: None declared, Tulika Chatterjee: None declared, Praggya Yaadav: None declared, Sreoshy Saha: None declared, Tsvetelina Velikova: None declared, Phonpen Akarawatcharangura Goo: None declared, Marcin Milchert: None declared, Yi-Ming Chen: None declared, Russka Shumnalieva: None declared, Roberto F. Caporali: None declared, Ioannis Parodis: None declared, Elena Nikiphorou Advisory boards for Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, Pfizer and Lilly, Chris Wincup: None declared, Samuel Katsuyuki Shinjo: None declared, Arvind Nune: None declared, James B. Lilleker: None declared, Ai Lyn Tan: None declared, Binit Vaidya: None declared, Dey Dzifa: None declared, Lina El Kibbi: None declared, Nelly Ziade: None declared, Abraham Edgar Gracia-Ramos: None declared, Syahrul Sazliyana Shaharir: None declared, Masataka Kuwana: None declared, Johannes Knitza: None declared, Carlo Vinicio Caballero: None declared, Miguel A. Saavedra: None declared, Lorenzo Cavagna: None declared, Oliver Distler: None declared, A T M Tanveer Hasan: None declared, Carlos Enrique Toro-Gutierrez: None declared, Hector Chinoy: None declared, Vikas Agarwal: None declared, Rohit Aggarwal: None declared, Latika Gupta: None declared

Tepotinib, a MET tyrosine kinase inhibitor, is approved for the treatment of advanced MET exon 14 (METex14) skipping NSCLC in several Asian countries. In the global VISION trial (Cohorts A+C; N=313), tepotinib demonstrated durable clinical activity with an objective response rate (ORR) of 51.4% and a median (m) duration of response (DOR) of 18.0 months in long-term follow-up (median 32.6 months; data cut-off: November 20, 2022). Here, we report outcomes in the subgroup of Asian patients.

Background Regional disparities in the management of systemic lupus erythematosus (SLE) are frequently described. Governance, funding, logistic barriers, and physician choice may be important determinants though scarce data from underrepresented regions limits our understanding. Objectives To evaluate global patterns in treatment of SLE and identify the prevalence of comorbidities. Methods We identified SLE patients from the COVAD 2 database, consisting of over 20,000 respondents worldwide. Healthy controls (HC) were included to assess population comorbidity levels. Demographics, treatment i.e., corticosteroids (CS), antimalarials, immunosuppressants (IS), cyclophosphamide and biologics plus comorbidity data was recorded. Country Human Development Index (HDI) classification, a composite index formulated by the United Nations to rank countries into tiers of development, was utilised. Results 3323 HCs and 1167 SLE patients were included in analysis. Patients from low/medium HDI (lmHDI) countries were younger than those from high/very high HDI (hvhHDI) countries (median age 32, IQR 27-41 vs 41, IQR 32-52 years, p<0.0001). Disease duration was shorter in lmHDI countries (median 5, IQR 3-10 vs 10, IQR 5-19 years, p<0.0001).A higher proportion of SLE patients from lmHDI countries were on CS (73% vs 59%, p=0.0002), antimalarials (81% vs 68%, p=0.0002) and IS (66% vs 53%, p=0.0009) compared with patients from hvhHDI countries. Choice of IS varied with azathioprine prescribed more frequently in lmHDI countries (p=0.049). Biologics use was more common in hvhHDI countries (7% vs 2%, p=0.0055). Comorbidity prevalence was similar between groups, however when adjusted for age, patients with chronic kidney disease were significantly younger in lmHDI countries (36.67 vs 44.64 years, p=0.015), as were patients with coronary artery disease (35.7 vs. 44.6 years, p=0.015) and hypertension (41.5 vs 49.8 years, p=0.003). Results are detailed in Table 1. Conclusion To our knowledge, this is the largest study evaluating treatment and comorbidity incidence in SLE populations based on country HDI. We identified striking differences in pharmacological management globally. Cardiovascular comorbidities were seen in younger patients and earlier in the disease course in lmHDI countries, suggestive of premature organ damage. This could be due to limited global access to high-cost medication and increasing access may improve outcomes. Our results call for review of cardiovascular risk guidelines and regional approaches to preventive action as well as pharmacological and non-pharmacological management of patients with established cardiovascular comorbidity. REFERENCES: NIL. Acknowledgements: NIL. Disclosure of Interests Amelia Holloway: None declared, Sook Yan Lee: None declared, Elena Nikiphorou Speakers bureau: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, Paid instructor for: Celltrion, Pfizer, Sanofi, Gilead, Galapagos, AbbVie, and Lilly, Grant/research support from: Pfizer and Lill, Ioannis Parodis Grant/research support from: has received research funding and/or honoraria from Amgen, AstraZeneca, Aurinia Pharmaceuticals, Elli Lilly and Company, Gilead Sciences, GlaxoSmithKline, Janssen Pharmaceuticals, Novartis and F. Hoffmann-La Roche AG., Naveen Ravichandran: None declared, Jessica Day Grant/research support from: has received research funding from CSL Limited, Mrudula Joshi: None declared, Sreoshy Saha: None declared, Syahrul Sazliyana Shaharir: None declared, Wanruchada Katchamart: None declared, Phonpen Akarawatcharangura Goo: None declared, Lisa Traboco: None declared, Yi-Ming Chen: None declared, Parikshit Sen: None declared, James B. Lilleker Speakers bureau: has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Consultant of: has received speaker honoraria/participated in advisory boards for Sanofi Genzyme, Roche, and Biogen. None is related to this manuscript., Arvind Nune: None declared, John Pauling: None declared, Ai Lyn Tan Speakers bureau: has received honoraria for advisory boards and speaking for Abbvie, Gilead, Janssen, Lilly, Novartis, Pfizer, and UCB., Nelly Ziade Speakers bureau: has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre; none are related to this manuscript., Consultant of: has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre; none are related to this manuscript., Grant/research support from: has received speaker fees, advisory board fees, and research grants from Pfizer, Roche, Abbvie, Eli Lilly, NewBridge, Sanofi-Aventis, Boehringer Ingelheim, Janssen, and Pierre Fabre; none are related to this manuscript., Marcin Milchert: None declared, Abraham Edgar Gracia-Ramos: None declared, Carlo Vinicio Caballero: None declared, Vikas Agarwal: None declared, Rohit Aggarwal Consultant of: Mallinckrodt, Octapharma, CSL Behring, Bristol Myers-Squibb, EMD Serono, Q32, Kezar, Pfizer, AstraZeneca, Alexion, Argenx, Boehringer Ingelheim (BI), Corbus, Janssen, Kyverna, Roivant, Merck, Galapagos, Actigraph, Scipher, Horizon Therapeutics, Teva, Beigene, ANI Pharmaceuticals, Biogen, Nuvig, Capella Bioscience, CabalettaBio, Grant/research support from: Mallinckrodt, Pfizer, Bristol Myers-Squibb, Q32, EMD Serono, Janssen, Boehringer Ingelheim (BI), Latika Gupta: None declared, Chris Wincup: None declared.Table 1Low HDI (n=50)Medium HDI (n=163)High HDI (n=265)Very High HDI (n=689)All SLE Patients (n=1167)p value (SLE lmHDI vs hvhHDI)Immunosuppressants, n (%)36 (72)104 (64)169 (64)339 (49)648 (56)0.0009***Methotrexate, n (%)5 (10)27 (17)35 (13)91 (13)158 (14)nsMycophenolate Mofetil, n (%)9 (18)45 (28)70 (26)127 (18)251 (22)nsAzathioprine, n (%)21 (42)32 (20)65 (25)113 (16)231 (20)0.049*Cyclophosphamide, n (%)0 (0)3 (2)2 (1)9 (1)14 (1)nsCorticosteroids, n (%)37 (74)119 (73)159 (60)404 (59)719 (62)0.0002***No Steroids, n (%)7 (14)20 (12)50 (19)92 (13)169 (15)ns<10 mg/day, n (%)17 (34)58 (36)89 (34)184 (27)348 (30)0.057 (ns)10-20 mg/day, n (%)9 (18)19 (12)20 (8)47 (7)95 (8)0.003**>20 mg/day, n (%)3 (6)7 (4)10 (4)16 (2)36 (3)nsAntimalarials, n (%)40 (80)133 (82)182 (69)469 (68)824 (71)0.0002***Biological treatments, n (%)1 (2)3 (2)19 (7)48 (7)71 (6)0.005**ComorbiditiesSLEHCSLEHCSLEHCSLEHCSLEHCChronic Kidney Disease, n (%)5* (10)0 (0)13* (8)7 (0.8)31* (12)5 (0.4)76* (11)4 (0.4)125* (11)16 (0.5)NsCoronary Heart disease, n (%)1 (2)1 (0.5)2 (1)8 (0.9)11* (4)6 (0.4)15 (2)15 (1.6)29* (2)30 (1)NsDiabetes, n (%)2 (4)11 (0.5)4 (2)51 (5.5)7 (3)33 (3)28 (4)29 (3)41 (4)124 (4)NsHypercholesterolaemia, n (%)2 (4)5 (2)6 (4)48 (5)17 (6)91 (7)75 (11)77 (8)100* (9)221 (7)0.0055**Hypertension, n (%)8 (16)28 (13)24 (15)95 (10)37* (14)122 (10)122* (18)77 (8)191 (16)212 (6)Ns

The combination of an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) with either bevacizumab or ramucirumab, both anti-angiogenic agents, has demonstrated superior efficacy in progression-free survival (PFS) than TKI monotherapy in EGFR-mutated non-small cell lung cancer (NSCLC). The clinical applications, efficacy, and adverse events of these two different dual combinations in real-world practice remain unknown.

Objectives We investigated coronavirus disease 2019 (COVID-19) vaccine safety in pregnant and breastfeeding women with autoimmune diseases (AID) in the COVID-19 Vaccination in Autoimmune Diseases (COVAD) study. Methods Delayed-onset (>7 days) vaccine-related adverse events (AE), disease flares and AID-related treatment modifications were analysed upon diagnosis of AID vs healthy controls (HC) and the pregnancy/breastfeeding status at the time of at least one dose of vaccine. Results Among the 9201 participants to the self-administered online survey, 6787 (73.8%) were women. Forty pregnant and 52 breastfeeding patients with AID were identified, of whom the majority had received at least one dose of COVID-19 vaccine (100% and 96.2%, respectively). AE were reported significantly more frequently in pregnant than in non-pregnant patients (overall AE 45% vs 26%, P = 0.01; minor AE 40% vs 25.9%, P = 0.03; major AE 17.5% vs 4.6%, P < 0.01), but no difference was found in comparison with pregnant HC. No difference was observed between breastfeeding patients and HC with respect to AE. Post-vaccination disease flares were reported by 17.5% of pregnant and 20% of breastfeeding patients, and by 18.3% of age- and disease-matched non-pregnant and non-breastfeeding patients (n = 262). All pregnant/breastfeeding patients who experienced a disease flare were managed with glucocorticoids; 28.6% and 20% of them required initiation or change in immunosuppressants, respectively. Conclusion This study provides reassuring insights into the safety of COVID-19 vaccines administered to women with AID during the gestational and post-partum periods, helping overcome hesitant attitudes, as the benefits for the mother and for the fetus by passive immunization appear to outweigh potential risks.

Background Rapidly progressive interstitial lung disease (RP-ILD) is often seen in dermatomyositis patients with anti-melanoma differentiation-associated gene 5 (anti-MDA-5) antibody. They often have a poor prognosis with rapid decline in pulmonary function, leading to respiratory failure (1). Aggressive immunosuppressive therapy has been reported with improved prognosis, however; it may lead to opportunistic infections, including cytomegalovirus (CMV) or Pneumocystis pneumonia (PCP) infection (2, 3). Objectives This study aimed to evaluate the effectiveness of tofacitinib (TOF) in combination with CMV and PCP prophylaxis in anti-MDA-5-positive patients. Methods Medical records of 17 anti-MDA-5-positive RP-ILD patients enrolled during Mar 2017 to May 2021 were reviewed. RP-ILD was defined by the presence of deteriorated dyspnea, with a decrease in PaO2 levels and emerging radiographic anomalies within 4 weeks without evidence of infection (4). Chest CT was scored using Ichikado score (5). Clinical parameters including ferritin levels, white counts (WBC), Lactate dehydrogenase (LDH) levels, GAP scores (Gender, Age, and Physiology score for idiopathic pulmonary fibrosis) were recorded. Medications included cyclophosphamide (CyP), intravenous immunoglobulin (IVIG), mycophenolic acid derivatives (MPA), rituximab (RTX), and calcineurin inhibitor (CNI). Kaplan-Meier survival analysis and Log-rank test were used to evaluate one-year mortality differences (MedCalc version 19.6). The Ethics Committee approved our study (CE17038B). Results Six anti-MDA-5-positive RP-ILD patients were treated with tofacitinib; five had concomitant CMV prophylaxis with valganciclovir (VGCV); 4 had PCP prophylaxis with trimethoprim/sulfamethoxazole (TMP-SMX). Patients’ demographic data are shown in Table 1. The median age, clinical manifestations, laboratory data, and chest CT scores were comparable between tofacitinib and non-tofacitinib groups. Prevalence of MPA use was higher in the non-TOF group. Kaplan-Meier survival analysis (Figure 1) indicated that patients with tofacitinib treatment (p=0.001), valganciclovir (p=0.003), and TMP-SMX (p=0.028) prophylaxis exhibited better 1-year survival rates compared with those without TOF therapy, VGCV, and TMP-SMX prophylaxis. Table 1. Clinical characteristics of anti-MDA-5 antibody-positive patients with RP-ILD receiving tofacitinib vs non-tofacitinib treatment. Tofacitinib (n=6) Non-tofacitinib (n=11) p value Age (years) 58 (42.3-77) 57 (50.0-62.0) 0.884 Female sex, n (%) 2 (33.3) 6 (54.5) 0.620 Diabetes mellitus, n (%) 0 (0) 5 (45.5) 0.102 Fever, n (%) 5 (83.3) 10 (90.9) 1.000 Mechanic’s hands, n (%) 4 (66.7) 5 (45.5) 0.620 Ferritin (n=16, ng/ml)) 2670.9 (719.7-4209.7) 1563.5 (967.8-3169.0) 0.635 WBC (x1000μl) 8.7 (6.5-9.9) 8.7 (6.0-12.9) 0.884 LDH (n=16, U/l) 367.0 (218.0-557.5) 433.0 (331.0-625.3) 0.313 GAP score 5 (2.5-8) 5 (2-6) 0.808 CT score 200.0 (124.2-214.2) 196.7 (153.3-273.3) 0.733 TMP-SMX, n (%) 4 (66.7) 0 (0) 0.006** VGCV, n (%) 5 (83.3) 0 (0) 0.001** CyP, n (%) 1 (16.7) 4 (36.4) 0.600 IVIG, n (%) 1 (16.7) 6 (54.5) 0.304 MPA, n (%) 0 (0) 7 (63.6) 0.035* RTX, n (%) 3 (50.0) 5 (45.5) 1.000 CNI, n (%) 2 (33.3) 6 (54.5) 0.620 Continuous variables were expressed as median (inter-quartile range). * p <0.05, ** p <0.01 by Mann–Whitney U test or Fisher’s Exact test. Figure 1. Conclusion The study demonstrated the efficacy of tofacitinib treatment in anti-MDA-5-positive RP-ILD. In addition, CMV and PCP prophylaxis appeared to improve in 1-year survival. Rheumatologists might consider TOF with prophylaxis as an option for anti-MDA-5-positive patients in daily practice. References [1]Sato S, et al. Arthritis Rheum 2009;60(7):2193-200. [2]Sekiguchi A, et al. J Dermatol 2020;47(8):876-81. [3]Sabbagh SE, et al. Rheumatology 2021;60(2):829-36. [4]Kurasawa K, et al. Rheumatology 2018;57(12):2114-19. [5]Ichikado K, et al. Radiology 2006;238(1):321-9. Acknowledgements We are grateful to the Biostatistics Task Force staff of Taichung Veterans General Hospital for their assistance in performing the statistical analyses and Tomoko Hasegawa for her technical assistance with the immunoassays. We also thank Dr. Wen-Nan Huang, Dr. Pin-Kuei Fu, Dr. Chia-Wei Hsieh, Dr. Yi-Hsing Chen, and Dr. Der-Yuan Chen for their help on resources and supervision. Disclosure of Interests None declared

Multiple studies have reported that retreatment with erlotinib is an alternative option for patients with epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) who had benefited from previous EGFR-tyrosine kinase inhibitor (TKI) therapy and progressed after chemotherapy. Dacomitinib is a second-generation EGFR-TKI for the first-line treatment of EGFR-mutant advanced NSCLC. The efficacy of dacomitinib in previously EGFR-TKI treated NSCLC remains unclear in real-world practice.

Pulmonary infection has been an important concern in patients with non-small cell lung cancer. It is well-known that chemotherapy may increase the infection rate by suppressing the immune system. Whether the clinical outcome of pulmonary infection is association with immunotherapy is still unclear. Mass cytometry is a next-generation flow cytometry platform with multiparametric analyses. Previous studies of mass cytometry showed that exhausted T cell were implicated in disease progression and response to immunotherapy.

Tepotinib, a MET TKI, is approved for METex14 skipping NSCLC in several Asian countries. In VISION (N=313; data cut-off: Feb 20, 2022), tepotinib demonstrated durable clinical activity with an objective response rate (ORR) of 50.8% and a median (m) duration of response (DOR) of 18.0 months. Tepotinib also showed promising intracranial activity in patients (pts) with brain metastases. We report data from all 106 Asian pts with METex14 skipping NSCLC enrolled in VISION.

IMpower010 (NCT02486718) was the first Phase III immunotherapy study to show a statistically significant disease-free survival (DFS) benefit with adjuvant atezolizumab vs best supportive care (BSC) in resected NSCLC following platinum-based chemotherapy (Felip et al. Lancet 2021). Based on these findings, atezolizumab was approved as adjuvant treatment after resection and platinum-based chemotherapy in patients with programmed death-ligand 1 (PD-L1) tumour cell (TC) ≥1% stage II-IIIA NSCLC in the US, China, and other countries; and in PD-L1 TC ≥50% stage II-IIIA NSCLC in the EU and other countries The key secondary OS endpoint was not mature at the IMpower010 DFS interim analysis (IA) but is of considerable clinical interest in this curative setting.

Tepotinib, an oral, once daily (QD), highly selective, potent MET inhibitor that has shown durable activity in pts with METex14 skipping advanced NSCLC, is approved in Japan. The phase II VISION study showed an overall objective response rate (ORR) of 44.5–47.4% by independent review (IRC), and 54.7–58.3% by investigator assessment (INV); onset of response was mostly observed within 6 weeks. Here, we report outcomes in Asian pts. Pts with advanced EGFR/ALK wild-type and METex14 skipping NSCLC, detected by liquid or tissue biopsy, received oral tepotinib 500 mg QD until disease progression, intolerable toxicity, or withdrawal of consent. The primary endpoint was objective response (OR) (confirmed by two scans ≥4 weeks apart) by IRC; secondary endpoints were OR by INV, duration of response (DOR), progression-free survival (PFS), and safety. Pts evaluable for ORR had ≥2 post-baseline assessments or discontinuation for any reason. At data cut-off (Jan 1, 2020), 38 pts evaluable for efficacy were Asian with a median age of 70 years (52–85), 32% female, 39% non-smokers, and 32% treatment naïve. Asian pts were enrolled from Japan (50%), Korea (26%), Taiwan (13%), Spain (3%), and the US (8%). Efficacy of tepotinib in Asian pts was similar to the overall population; ORR (95% CI) was 47.4% (31.0, 64.2) by IRC (median DOR [mDOR] was not reached) and 60.5% (43.4, 76.0) by INV (mDOR was 10.9 months [9.7, ne]). Disease control rate (confirmed complete or partial response, or stable disease lasting ≥12 weeks) was 68.4% (51.3, 82.5) by IRC and 81.6% (65.7, 92.3) by INV. Although still immature, median PFS (95% CI) was 11.0 months (4.9, ne). Overall, 50 Asian pts received at least one dose of tepotinib. The most common adverse events (any cause) were peripheral edema, increased blood creatinine, and diarrhea. Grade ≥3 treatment-related adverse events (TRAEs) were observed in 26% of pts. TRAEs led to dose reductions in 28%, temporary discontinuation in 36%, and permanent discontinuation in 10% of pts. Tepotinib showed robust, durable clinical activity in Asian pts with METex14 skipping NSCLC. Adverse events were mostly mild and manageable, with few discontinuations. The VISION study will enroll pts at 55 sites in Asia.