Search

Background/Aim: This study aimed at contributing to a better diagnosis of lung cancer by analyzing the patient’s symptoms and their linkage to other characteristics. Patients and Methods: We analyzed the data of 3,322 patients from LUCAS (LUngCAncerfocuS) National Registry of the Czech Republic. Overall survival was assessed using the Kaplan–Meier method. Results: The most common symptoms were cough (47.5%), dyspnea (45.6%), pain (27.3%), and weight loss (25.7%). Among all patients, 16% were asymptomatic. We demonstrated the negative prognostic significance of increasing number of lung cancer symptoms, that was significant after adjustment for age, TNM stages, and performance status, and morphological types of the cancer. Conclusion: Monitoring the severity and type of symptoms in patients with lung cancer can help in the diagnostics of the disease and the estimation of prognosis.

Background Data regarding real‐life effectiveness of any treatment may improve clinical decision‐making. The aim of this study was to evaluate real‐life effectiveness of tyrosin‐kinase inhibitors, bevacizumab and pemetrexed as first‐line treatments in patients with advanced/metastatic non‐small cell lung cancer (NSCLC). Methods We analyzed data of 2157 patients of the Czech TULUNG Registry of patients with advanced/metastatic NSCLC who received modern‐era treatments between 2011 and 2018. Patients treated with gefitinib, erlotinib, afatinib, bevacizumab (+ maintenance), pemetrexed (+ maintenance) as first‐line therapy were included in the study. A systematic literature search separately identified clinical trials suitable for calculation of comparator pooled OS and PFS for each regimen. For each subgroup, basic characteristics and survival data (Kaplan‐Meier estimates) are shown. We propose the “index of real‐life effectiveness” (IRE), a ratio of real‐life OS/PFS and comparator pooled OS/PFS. Univariate and multivariate logistic regression identified factors were associated with longer OS (ie, IRE>1.1). Results Survival analysis showed median OS of 23 months for erlotinib, 29.3 months for afatinib, 19.6 months for gefitinib, 12.2 months for pemetrexed, 17.5 months for pemetrexed maintenance, 15.8 months for bevacizumab and 15.8 months for bevacizumab maintenance. Calculated IREs for OS for the regimens were: erlotinib 1.013, afatinib 1.184, gefitinib 0.736, pemetrexed 1.188, pemetrexed maintenance 1.294, bevacizumab 1.178, and bevacizumab maintenance 1.189. Multivariate regression analysis showed that these factors were associated with longer OS: lower PS for afatinib; lower PS, absence of adverse events and female sex for bevacizumab; and lower PS and female sex for pemetrexed. Conclusions This study clearly demonstrated that real‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems, and comparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens. Lower ECOG PS, younger age, female sex and adverse events were associated with longer survival in most regimens. Key points Significant findings of the study Comparison between TULUNG data and pooled survival data from trials showed higher real‐life effectiveness for most of the studied first‐line regimens; for most regimens, lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. What this study adds Real‐life effectiveness of certain treatment regimens may strongly differ in various populations/health care systems., Comparison between our TULUNG data and pooled survival data from clinical trials showed higher real‐life effectiveness for most of the studied first‐line regimens. We found that lower ECOG PS, younger age, female sex and adverse events were associated with longer survival. We demonstrated that real‐life effectiveness of certain treatments may strongly differ in various populations and health care systems.

Cilena lecba a imunoterapie jsou nezpochybnitelným standardem lecby již v prvni linii NSCLC. Pro rozhodnuti o lecbě NSCLC jezasadni znalost výsledků prediktivniho testovani u vsech nemocných, stanoveni prediktivnich biomarkerů je nedilnou soucastidiagnozy NSCLC. Pro zlepseni prognozy nemocných s NSCLC je potřebne zajistit precizni diagnostiku, ktera umožni identifikacinemocných vhodných pro cilenou lecbu a imunoterapii. Nastaveni efektivni spoluprace pracovisť mimo centra s Komplexnimionkologickými centry zvýsi dostupnost nových leků pro pacienty s NSCLC.

Background Enhancing tumor-specific T-cell immunity by inhibiting programmed death ligand 1 (PD-L1)–programmed death 1 (PD-1) signaling has shown promise in the treatment of extensive-stag...

Background: Immune checkpoint inhibitors are a new standard of care for patients with advanced non-small-cell lung cancer (NSCLC) without EGFR tyrosine kinase or anaplastic lymphoma kinase (ALK) genetic aberrations (EGFR−/ALK−), but clinical benefit in patients with EGFR mutations or ALK rearrangements (EGFR+/ALK+) has not been shown. We assessed the effect of durvalumab (anti-PD-L1) treatment in three cohorts of patients with NSCLC defined by EGFR/ALK status and tumour expression of PD-L1. Methods: ATLANTIC is a phase 2, open-label, single-arm trial at 139 study centres in Asia, Europe, and North America. Eligible patients had advanced NSCLC with disease progression following at least two previous systemic regimens, including platinum-based chemotherapy (and tyrosine kinase inhibitor therapy if indicated); were aged 18 years or older; had a WHO performance status score of 0 or 1; and measurable disease per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Key exclusion criteria included mixed small-cell lung cancer and NSCLC histology; previous exposure to any anti-PD-1 or anti-PD-L1 antibody; and any previous grade 3 or worse immune-related adverse event while receiving any immunotherapy agent. Patients in cohort 1 had EGFR+/ALK+ NSCLC with at least 25%, or less than 25%, of tumour cells with PD-L1 expression. Patients in cohorts 2 and 3 had EGFR−/ALK− NSCLC; cohort 2 included patients with at least 25%, or less than 25%, of tumour cells with PD-L1 expression, and cohort 3 included patients with at least 90% of tumour cells with PD-L1 expression. Patients received durvalumab (10 mg/kg) every 2 weeks, via intravenous infusion, for up to 12 months. Retreatment was allowed for patients who benefited but then progressed after completing 12 months. The primary endpoint was the proportion of patients with increased tumour expression of PD-L1 (defined as ≥25% of tumour cells in cohorts 1 and 2, and ≥90% of tumour cells in cohort 3) who achieved an objective response, assessed in patients who were evaluable for response per independent central review according to RECIST version 1.1. Safety was assessed in all patients who received at least one dose of durvalumab and for whom any post-dose data were available. The trial is ongoing, but is no longer open to accrual, and is registered with ClinicalTrials.gov, number NCT02087423. Findings: Between Feb 25, 2014, and Dec 28, 2015, 444 patients were enrolled and received durvalumab: 111 in cohort 1, 265 in cohort 2, and 68 in cohort 3. Among patients with at least 25% of tumour cells expressing PD-L1 who were evaluable for objective response per independent central review, an objective response was achieved in 9 (12·2%, 95% CI 5·7–21·8) of 74 patients in cohort 1 and 24 (16·4%, 10·8–23·5) of 146 patients in cohort 2. In cohort 3, 21 (30·9%, 20·2–43·3) of 68 patients achieved an objective response. Grade 3 or 4 treatment-related adverse events occurred in 40 (9%) of 444 patients overall: six (5%) of 111 patients in cohort 1, 22 (8%) of 265 in cohort 2, and 12 (18%) of 68 in cohort 3. The most common treatment-related grade 3 or 4 adverse events were pneumonitis (four patients [1%]), elevated gamma-glutamyltransferase (four [1%]), diarrhoea (three [1%]), infusion-related reaction (three [1%]), elevated aspartate aminotransferase (two [

OZGUROGLU, MUSTAFA/0000-0002-8417-8628 WOS:000579504300008 PubMed ID: 32961445 Objectives: In the phase III CASPIAN study, first-line durvalumab plus etoposide in combination with either cisplatin or carboplatin (EP) significantly improved overall survival (primary endpoint) versus EP alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) at the interim analysis. Here we report patient-reported outcomes (PROs). Materials and methods: Treatment-naive patients with ES-SCLC received 4 cycles of durvalumab plus EP every 3 weeks followed by maintenance durvalumab every 4 weeks until progression, or up to 6 cycles of EP every 3 weeks. PROs, assessed with the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire-Core 30 (QLQ-C30) version 3 and its lung cancer module, the Quality of Life Questionnaire-Lung Cancer 13 (QLQ-LC13), were prespecified secondary endpoints. Changes from baseline to disease progression or 12 months in prespecified key disease-related symptoms (cough, dyspnea, chest pain, fatigue, appetite loss) were analyzed with a mixed model for repeated measures. Time to deterioration (TTD) of symptoms, functioning, and global health status/quality of life (QoL) from randomization was analyzed. Results: In the durvalumab plus EP and EP arms, 261 and 260 patients were PRO-evaluable. Patients in both arms experienced numerically reduced symptom burden over 12 months or until progression for key symptoms. For the improvements from baseline in appetite loss, the between-arm difference was statistically significant, favoring durvalumab plus EP (difference, 4.5; 99% CI: 9.04, 0.04; nominal p = 0.009). Patients experienced longer TTD with durvalumab plus EP versus EP for all symptoms (hazard ratio [95% CI] for key symptoms: cough 0.78 [0.600-1.026]; dyspnea 0.79 [0.625-1.006]; chest pain 0.76 [0.575-0.996]; fatigue 0.82 [0.653-1.027]; appetite loss 0.70 [0.542-0.899]), functioning, and global health status/QoL. Conclusion: Addition of durvalumab to first-line EP maintained QoL and delayed worsening of patient-reported symptoms, functioning, and global health status/QoL compared with EP. AstraZenecaAstraZeneca The study was funded by AstraZeneca.

A 61-year-old Caucasian female patient presented to her general practitioner complaining of progressive diminished visual acuity, narrowed visual field and blurred vision in her right eye. She had a history of hepatic steatosis, arterial hypertension and bronchial asthma in childhood. She reported no alcohol abuse and was a former smoker (1 pack-year history of smoking, with more than 30 years smoke-free)., Can you diagnose this patient with vision problems? https://bit.ly/3vGe5qy

Aim: To compare survival outcomes in patients with non-small cell lung cancer (NSCLC) treated with modern-era drugs (antifolates, antiangiogenics, tyrosine kinase and anaplastic lymphoma kinase inhibitors, immunotherapy) with treatment initiation in 2011-12 and 2015-16, respectively. Patients and Methods: Prospective data from Czech TULUNG Registry (960 patients from 2011-12 and 512 patients from 2015-16) were analyzed. Kaplan-Meier analysis was used to estimate overall survival (OS) and progression free survival (PFS); Cox proportional hazards model to assess factors associated with 2-year survival. Results: Survival at 2 years was more frequent in cohort 2015-16 compared to cohort 201112 (43.2% vs. 24% for adenocarcinoma; p

Background Immunotherapy with or without chemo has improved survival vs chemo in 1L aNSCLC. NIVO + chemo showed encouraging activity in a phase 1 study in this setting. CheckMate 227 is a multi-part, randomized, open-label, phase 3 study evaluating NIVO-based regimens vs chemo. We present final results from Part 2, which evaluated NIVO + chemo vs chemo in 1L aNSCLC. Methods Pts (N = 755) with chemo-naive, stage IV or recurrent NSCLC, ECOG PS 0–1, and no sensitizing EGFR/ALK alterations were randomized 1:1 to receive every 3 weeks NIVO 360 mg + chemo or chemo. Pts were stratified by histology (squamous [SQ] vs non-squamous [NSQ]), sex, and PD-L1 expression ( Results Baseline characteristics were generally balanced. Minimum follow-up was 19.5 mo. In pts with NSQ NSCLC, no statistically significant improvement in OS was seen with NIVO + chemo vs chemo (HR, 0.86 [95.62% CI, 0.69–1.08; P=0.1859]); median OS was 18.8 mo vs 15.6 mo; 12-mo OS rates were 67.3% vs 59.2%. HR for OS was 0.81 (95% CI, 0.67–0.97) in all randomized pts; 0.69 (95% CI, 0.50–0.97) in pts with SQ NSCLC. Progression-free survival and objective response rates favored NIVO + chemo in NSQ, SQ, and all randomized pts (table). Grade 3–4 tx-related adverse events occurred in 45% and 35% of all pts treated with NIVO + chemo and chemo, respectively.TableLBA3 Efficacy outcomes with 1L NIVO + chemo vs chemo in pts with NSQ NSCLC, SQ NSCLC, and in all randomized ptsTableNSQ NSCLCSQ NSCLCAll Randomized PtsNIVO + chemoChemoNIVO + chemoChemoNIVO + chemoChemon=270n = 273n=107n = 105n=377n = 378OSEvents, n (%)156 (57.8)164 (60.1)68 (63.6)75 (71.4)224 (59.4)239 (63.2)Median, mo18.815.618.312.018.314.7HR (95% CI)0.86 (0.69–1.08)aP = 0.18590.69 (0.50–0.97)0.81 (0.67–0.97)12-mo OS rate, %67.359.266.148.566.956.2PFSEvents, n (%)187 (69.3)200 (73.3)79 (73.8)82 (78.1)266 (70.6)282 (74.6)Median, mo8.75.87.14.48.45.5HR (95% CI)0.67 (0.55–0.82)0.51 (0.37–0.70)0.62 (0.52–0.73)12-mo PFS rate, %39.525.731.79.337.321.3Objective response rate, n (%)130 (48.1)80 (29.3)64 (59.8)34 (32.4)194 (51.5)114 (30.2)a95.62% CI Conclusion CheckMate 227 Part 2 did not meet the primary endpoint of OS for NIVO + chemo vs chemo in NSQ NSCLC. Descriptive analyses showed longer OS with NIVO + chemo in all randomized pts and SQ NSCLC. No new safety signals were observed. Clinical trial identification NCT02477826; Release date: June 23, 2015. Editorial acknowledgement Writing and editorial assistance was provided by Namiko Abe, PhD, of Caudex, funded by Bristol-Myers Squibb. Legal entity responsible for the study Bristol-Myers Squibb. Funding Bristol-Myers Squibb. Disclosure L. Paz-Ares: Honoraria (self): Roche, MSD, Lilly, Novartis, Boehringer Ingelheim, AstraZeneca, Amgen, Sanofi, Pharmamar, Pfizer, Bristol-Myers Squibb, Merck, Takeda, Celgene, Servier, Sysmex, Incyte, Ipsen, Adacap, Bayer, Blueprint; Leadership role: Altum Sequencing; Research grant / Funding (institution): MSD, AstraZeneca, Pfizer, Bristol-Myers Squibb; Officer / Board of Directors: Genomica. T.E. Ciuleanu: Advisory / Consultancy: Astellas, Janssen, Bristol-Myers Squibb, Merck Serono, Amgen, Roche, Pfizer, Boehringer Ingelheim, Lilly, AstraZeneca, MSD, Sanofi, Novartis, Servier, AD Pharma. A. Pluzanski: Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Speaker Bureau / Expert testimony: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche, Takeda; Travel / Accommodation / Expenses: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, MSD, Roche. A. Nagrial: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche; Research grant / Funding (institution): Astra Zeneca, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche. R. Kowalyszyn: Advisory / Consultancy: Astellas, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, MSD, Novartis; Research grant / Funding (institution): Novartis; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Lilly, MSD, Pfizer, Roche. C. Audigier-Valette: Honoraria (self): AbbVie, Pfizer; Honoraria (institution): Roche, MSD, Bristol-Myers Squibb, AstraZeneca; Advisory / Consultancy: Roche, MSD, Bristol-Myers Squibb, AstraZeneca, AbbVie, Pfizer. Y-L. Wu: Honoraria (self): AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche; Advisory / Consultancy: AstraZeneca, Boehringer Ingelheim, Roche; Research grant / Funding (institution): AstraZeneca, Boehringer Ingelheim, BMS, Roche; Non-remunerated activity/ies: AstraZeneca, Boehringer Ingelheim, BMS, Eli Lilly, MSD, Pfizer, Roche. H. Borghaei: Honoraria (self): University of Pennsylvania, CAR T Program, Takeda [Data and Safety Monitoring Board]; Advisory / Consultancy: Bristol-Myers Squibb, Lilly, Genentech, Celgene, Pfizer, Merck, EMD-Serono, Boehringer Ingelheim, AstraZeneca, Novartis, Genmab, Regeneron, BioNTech, Cantargia AB, Amgen, AbbVie, Axiom, PharmaMar, Takeda, Huya Bio, GLG; Research grant / Funding (self): Millennium, Merck/Celgene, Bristol-Myers Squibb/Lilly. M.D. Hellmann: Advisory / Consultancy: Genentech, Bristol-Myers Squibb, Merck, AstraZeneca, Novartis, Janssen, Mirati, Syndax, Shattuck Labs, Immunai, Nektar, Blueprint Medicines; Research grant / Funding (institution): Bristol-Myers Squibb; Travel / Accommodation / Expenses: Bristol-Myers Squibb, AstraZeneca; Shareholder / Stockholder / Stock options: Shattuck Labs, Immunai. J. Brahmer: Advisory / Consultancy: Bristol-Myers Squibb, AstraZeneca, Genentech, Merck, Amgen. M. Reck: Honoraria (self): AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche; Advisory / Consultancy: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly, Merck, MSD, Novartis, Pfizer, Roche. S. Ramalingam: Honoraria (self): AstraZeneca, Bristol-Myers Squibb, Roche/Genentech, Loxo, Tesaro, Merck, Daichi; Advisory / Consultancy: Amgen, AbbVie, Lilly, Genentech, Takeda; Research grant / Funding (institution): Bristol-Myers Squibb, Amgen, AstraZeneca, Takeda, Advaxis, Tesaro, Merck. L. Zhang: Advisory / Consultancy: AstraZeneca, Bristol-Myers Squibb, MSD; Speaker Bureau / Expert testimony: AstraZeneca, Bristol-Myers Squibb, MSD, Roche; Research grant / Funding (institution): AstraZeneca, Bristol-Myers Squibb, Pfizer, Henrui Pharm. P. Bhagavatheeswaran: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. F.E. Nathan: Shareholder / Stockholder / Stock options, Full / Part-time employment: Bristol-Myers Squibb. K.J. O'Byrne: Advisory / Consultancy: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Novartis, Teva, Janssen-Cilag, Natera; Speaker Bureau / Expert testimony: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim, Janssen-Cilag, Mundipharma; Travel / Accommodation / Expenses: Bristol-Myers Squibb, Pfizer, AstraZeneca, MSD, Roche-Genentech, Boehringer Ingelheim; Shareholder / Stockholder / Stock options: Carp Pharmaceuticals, Carpe Vitae Phaemaceuticals; Licensing / Royalties: Various patents issues with licensee as listed. Queensland University of Technology and Trinity College Dublin. All other authors have declared no conflicts of interest.

Background CASPIAN is an open-label, phase III study of first-line durvalumab (D), ± tremelimumab (T), plus etoposide and either cisplatin or carboplatin (EP) for the treatment of pts with ES-SCLC. In a planned interim analysis (IA), D+EP significantly improved OS vs EP alone (primary endpoint; HR 0.73 [95% CI 0.59–0.91]; p = 0.0047). We report prespecified exploratory results at this IA for pts recruited in Asia. Methods Treatment-naive pts with ES-SCLC were randomised (1:1:1) to D 1500 mg + EP q3w; D 1500 mg + T 75 mg + EP q3w; or EP q3w. Pts in the immunotherapy arms received up to 4 cycles of EP followed by maintenance D q4w until progression. Pts in the EP arm received up to 6 cycles of EP and PCI (investigator’s discretion). Investigator’s choice of cisplatin or carboplatin (stratification factor) was permitted. Data cutoff: 11 March 2019. Results Of the 537 pts in the D+EP and EP arms, 76 (14.2%) were randomised in Japan, South Korea, Taiwan or China (Asia subgroup). Some differences were observed in baseline characteristics between the Asia subgroup and overall population. Median OS for D+EP vs EP in the Asia subgroup was 14.8 vs 11.9 months (HR 0.87 [95%CI 0.45, 1.64]). More pts in the Asia subgroup vs the overall population received subsequent anticancer therapy (63.2 vs 43.2%; balanced between arms). Incidence of any cause SAEs was higher in the Asia subgroup vs the overall population regardless of treatment; AEs leading to discontinuation was less. In the Asia subgroup, for D+EP vs EP, the incidence of any cause grade 3/4 AEs was 62.9 vs 76.9%; respective incidences of SAEs and AEs leading to discontinuation were: 42.9 vs 48.7% and 5.7 vs 7.7%. The D+T+EP arm continues to final analysis. Table . LBA15 Durvalumab + EP EP Overall (n = 268) Asia subgroup (n = 35) Overall (n = 269) Asia subgroup (n = 41) Baseline characteristics Median age, years (range) 62 (28–82) 65 (40–82) 63 (35–82) 67 (46–82) Male, % 70.9 85.7 68.4 82.9 Ever/never smoker, % 91.8/8.2 97.1/2.9 94.4/5.6 95.1/4.9 WHO PS 0/1, % 36.9/63.1 31.4/68.6 33.5/66.5 19.5/80.5 Disease stage III/IV, % 10.4/89.6 11.4/88.6 8.9/91.1 2.4/97.6 OS Median OS, mo (95% CI) 13.0 (11.5–14.8) 14.8 (10.3–NR) 10.3 (9.3–11.2) 11.9 (8.0–18.9) OS HR * (95% CI) 0.73 (0.59–0.91) p = 0.0047 † 0.87 (0.45–1.64) - - 18-mo OS rate, % (95% CI) 33.9 (26.9–41.0) 39.2 (19.9–58.2) 24.7 (18.4–31.6) 32.1 (14.6–51.1) * Stratified Cox proportional hazards; † Primary endpoint Conclusions In the CASPIAN overall population, D+EP improved OS vs EP; results were consistent in this prespecified subgroup of patients recruited in Asia. The safety profile of D+EP in the Asia subgroup was also consistent with the overall population, with no new signals identified. Clinical trial identification NCT03043872 (Release date, 6 February 2017) EudraCT number: 2016-001203-23. Editorial acknowledgement Rebecca Douglas, PhD of Cirrus Communications (Macclesfield, UK), an Ashfield company, funded by AstraZeneca. Legal entity responsible for the study AstraZeneca PLC. Funding AstraZeneca. Disclosure M. Nishio: Honoraria (self): Ono Pharmaceutical; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Pfizer; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): Novartis; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Sankyo Healthcare; Honoraria (self): Merck Serono; Research grant/Funding (self): Ono Pharmaceutical; Research grant/Funding (self): Bristol-Myers Squibb; Research grant/Funding (self): Pfizer; Research grant/Funding (self): Chugai Pharmaceutical; Research grant/Funding (self): Eli Lilly; Research grant/Funding (self): Taiho Pharmaceutical; Research grant/Funding (self): AstraZeneca; Research grant/Funding (self): MSD; Research grant/Funding (self): Novartis; Research grant/Funding (self): Astellas, All outside the submitted work. K. Hotta: Research grant / Funding (self), Grants and personal fees: AstraZeneca / Lilly / Bristol-Myers Squibb; Travel / Accommodation / Expenses, Personal fees: MSD / Ono / Nipponkayaku / Taiho / Boehringer Ingelheim / Chugai. C-H. Chiu: Honoraria (self): AstraZeneca; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Merck Sharp & Dohme; Honoraria (self): Novartis; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Pfizer; Honoraria (self): Roche; Honoraria (self): Takeda. K. Azuma: Honoraria (self), Lecture fees: Ono Pharmaceutical Co Ltd / Bristol-Myers Squibb / AstraZeneca KK / Chugai Pharmaceutical. M. Ozguroglu: Advisory / Consultancy: Janssen / Sanofi / Astellas; Honoraria (self): Novartis / Roche / Janssen / Sanofi / Astellas; Travel / Accommodation / Expenses: Bristol-Myers Squibb / Janssen. J. Bar: Research grant / Funding (institution): MSD / AstraZeneca / Roche / BMS / Takeda / AbbVie / Pfizer; Travel / Accommodation / Expenses, Personal fees: AstraZeneca / MSD / Boehringer Ingelheim / Roche / BMS / Takeda / AbbVie / Pfizer / VBL. Y. Chen: Research grant / Funding (self): AstraZeneca / Ipsen / Roche / Bristol-Myers Squibb; Travel / Accommodation / Expenses, Personal fees: AstraZeneca / Genentech / Bristol-Myers Squibb / Merck / Novartis / Takeda / Eli Lilly / Guardant Health / Pfizer / Array Biopharma. J.W. Goldman: Research grant / Funding (self): AstraZeneca/MedImmune / Eli Lilly / Genentech / Bristol-Myers Squibb / Array BioPharma; Research grant / Funding (self): Celgene / AbbVie; Advisory / Consultancy: AstraZeneca / Genentech; Advisory / Consultancy: Lilly; Speaker Bureau / Expert testimony, Speakers' Bureau: Merck. N. Byrne: Full / Part-time employment, Contractor: AstraZeneca; Shareholder / Stockholder / Stock options: AstraZeneca. P.J. Laud: Full/Part-time employment: AstraZeneca, Contractor. N. Shire: Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: AstraZeneca. L. Paz-Ares: Honoraria (self): Roche/Genentech / Lilly / Pfizer/ Boehringer Ingelheim / BMS / MSD / AstraZeneca / Merck Serono; Honoraria (self): PharmaMar / Novartis / Celgene / Sysmex / Amgen / Incyte; Travel / Accommodation / Expenses: Roche / AstraZeneca / AstraZeneca Spain / MSD / BMS / Lilly / Pfizer; Leadership role, Myself: Genomica; Leadership role, An immediate family member: European Medicines Agency; Spouse / Financial dependant, Other relationship: Novartis / Ipsen / Pfizer / Servier / Sanofi / Roche / Amgen / Merck.

Background In the phase III CASPIAN trial, durvalumab (D) in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved the primary endpoint of OS vs EP alone in pts with extensive-stage small-cell lung cancer (ES-SCLC). Here we describe clinically relevant analyses for D + EP vs EP based on PD-L1 expression, progression patterns and PROs. Methods Tx-naive ES-SCLC (WHO PS 0/1) pts received 4 cycles of EP plus D q3w followed by maintenance D q4w or up to 6 cycles of EP q3w + prophylactic cranial irradiation (PCI; investigator's discretion). PD-L1 expression in optional archival tissue was tested by VENTANA PD-L1 (SP263) immunohistochemistry assay. PROs were assessed using EORTC QLQ-C30/LC13 with changes from baseline analysed by time to deterioration (TTD) per Cox proportional hazards. Results As of 11 March 2019, 265 and 266 pts had received D + EP and EP, respectively. Of 277 with evaluable samples (D + EP, 151; EP, 126), PD-L1 expression was low (5% and 22% of pts with expression ≥1% in tumour (TC) and immune cells (IC), respectively). Evaluating PD-L1 expression as a continuous variable in either TC or IC indicated no significant impact of PD-L1 on Tx effect between arms for OS (P=0.54 and 0.23, respectively); nor for PFS and ORR. Progression patterns were similar, although fewer pts developed new lesions at first progression with D + EP vs EP (41.4% vs 47.2%), including lung lesions (8.6% vs 15.2%). The incidence of new brain/CNS metastases was similar between arms (11.6% vs 11.5%), despite PCI allowance in the control arm only. Baseline PRO scores were comparable across all symptoms and functional domains. TTD was longer across all PROs for D + EP (favourable HRs, many with upper 95% CIs Conclusions D + EP provided significant OS benefit over EP alone, while preserving QoL and increasing the time to worsening of symptoms and functioning. PD-L1 expression was low and did not appear to be a predictive biomarker for D + EP. Clinical trial identification NCT03043872 (release date: February 6, 2017). Editorial acknowledgement Medical writing support was provided by Andrew Gannon, MA, MS, of Cirrus Communications (New York, NY), an Ashfield company, and funded by AstraZeneca. Legal entity responsible for the study AstraZeneca PLC. Funding AstraZeneca PLC. Disclosure L. Paz-Ares: Leadership role: Genomica; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Pfizer; Honoraria (self), Spouse / Financial dependant: Novartis; Spouse / Financial dependant: Ipsen; Spouse / Financial dependant: SERVIER; Spouse / Financial dependant: Sanofi; Honoraria (self), Spouse / Financial dependant: Amgen; Honoraria (self), Spouse / Financial dependant: Merck; Honoraria (self): Boehringer Ingelheim; Honoraria (self): PharmaMar; Honoraria (self): Celgene; Honoraria (self): Sysmex; Honoraria (self): Incyte. J.W. Goldman: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AbbVie. M.C. Garassino: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self): Roche. K. Hotta: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Ono; Honoraria (self): Nipponkayaku; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai. N. Reinmuth: Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Bohrigner Ingelheim; Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Hoffmann-La Roche; Honoraria (self): MSD SHARP & DOHME GMBH; Honoraria (self): Takeda; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Pfizer. Y. Shrestha: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Patel: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Mann: Full / Part-time employment: AstraZeneca. H. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Ozguroglu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Travel / Accommodation / Expenses: BMS. Y. Chen: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genetech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Brystol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: Eli-Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: Guardant Health; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Array Biopharma; Research grant / Funding (institution): ISPEN; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

Purpose To investigate the efficacy and safety of an active cellular immunotherapy (DCVAC/LuCa) and chemotherapy in patients with stage IV non-small cell lung cancer (NSCLC). Patients and Methods SLU01 was a multicenter, open-label, parallel-group, randomized, phase I/II trial. NSCLC patients were randomized in a ratio of 1:1:1 to receive: DCVAC/LuCa and chemotherapy (carboplatin and paclitaxel; Group A); DCVAC/LuCa, chemotherapy, pegylated interferon-α2b, and hydroxychloroquine (Group B); or chemotherapy alone (Group C). DCVAC/LuCa was administered subcutaneously every 3–6 weeks (up to 15 doses). The primary endpoint was overall survival (OS). During the study, enrollment into Group B was discontinued for strategic reasons. Results Forty-five patients were randomized to Group A, 29 patients to Group B, and 38 patients to Group C. The median OS in the modified intention-to-treat (mITT) population was 3.7 months longer in Group A than in Group C (15.5 vs. 11.8 months; p = 0.0179; hazard ratio = 0.54; 95% confidence interval: 0.32–0.91). This OS effect was consistent across subgroups of the mITT population (females, males, current smokers, former smokers, and patients with non-squamous and squamous cell histology). The most common treatment-emergent adverse events of any grade reported in Groups A, B, and C, respectively, were neutropenia (50.0%, 29.6%, and 20.6%), fatigue (40.0%, 18.5%, and 20.6%), anemia (35.0%, 44.4%, and 32.4%), paresthesia (27.5%, 25.9%, and 17.6%), and alopecia (25.0%, 29.6%, and 41.2%). Conclusion DCVAC/LuCa in combination with carboplatin and paclitaxel extended OS and was well tolerated.

Summary Background Fewer than half of the patients with completely resected non-small-cell lung cancer (NSCLC) are cured. Since the introduction of adjuvant chemotherapy in 2004, no substantial progress has been made in adjuvant treatment. We aimed to assess the efficacy of the MAGE-A3 cancer immunotherapeutic in surgically resected NSCLC. Methods In this randomised, double-blind, placebo-controlled trial, we recruited patients aged at least 18 years with completely resected stage IB, II, and IIIA MAGE-A3-positive NSCLC who did or did not receive adjuvant chemotherapy from 443 centres in 34 countries (Europe, the Americas, and Asia Pacific). Patients were randomly assigned (2:1) to receive 13 intramuscular injections of recMAGE-A3 with AS15 immunostimulant (MAGE-A3 immunotherapeutic) or placebo during 27 months. Randomisation and treatment allocation at the investigator site was done centrally via internet with stratification for chemotherapy versus no chemotherapy. Participants, investigators, and those assessing outcomes were masked to group assignment. A minimisation algorithm accounted for the number of chemotherapy cycles received, disease stage, lymph node sampling procedure, performance status score, and lifetime smoking status. The primary endpoint was broken up into three co-primary objectives: disease-free survival in the overall population, the no-chemotherapy population, and patients with a potentially predictive gene signature. The final analyses included the total treated population (all patients who had received at least one treatment dose). This trial is registered with ClinicalTrials.gov, number NCT00480025. Findings Between Oct 18, 2007, and July 17, 2012, we screened 13 849 patients for MAGE-A3 expression; 12 820 had a valid sample and of these, 4210 (33%) had a MAGE-A3-positive tumour. 2312 of these patients met all eligibility criteria and were randomly assigned to treatment: 1515 received MAGE-A3 and 757 received placebo and 40 were randomly assigned but never started treatment. 784 patients in the MAGE-A3 group also received chemotherapy, as did 392 in the placebo group. Median follow-up was 38·1 months (IQR 27·9–48·4) in the MAGE-A3 group and 39·5 months (27·9–50·4) in the placebo group. In the overall population, median disease-free survival was 60·5 months (95% CI 57·2–not reached) for the MAGE-A3 immunotherapeutic group and 57·9 months (55·7–not reached) for the placebo group (hazard ratio [HR] 1·02, 95% CI 0·89–1·18; p=0·74). Of the patients who did not receive chemotherapy, median disease-free survival was 58·0 months (95% CI 56·6–not reached) in those in the MAGE-A3 group and 56·9 months (44·4–not reached) in the placebo group (HR 0·97, 95% CI 0·80–1·18; p=0·76). Because of the absence of treatment effect, we could not identify a gene signature predictive of clinical benefit to MAGE-A3 immunotherapeutic. The frequency of grade 3 or worse adverse events was similar between treatment groups (246 [16%] of 1515 patients in the MAGE-A3 group and 122 [16%] of 757 in the placebo group). The most frequently reported grade 3 or higher adverse events were infections and infestations (37 [2%] in the MAGE-A3 group and 19 [3%] in the placebo group), vascular disorders (30 [2%] vs 17 [3%]), and neoplasm (benign, malignant, and unspecified (29 [2%] vs 16 [2%]). Interpretation Adjuvant treatment with the MAGE-A3 immunotherapeutic did not increase disease-free survival compared with placebo in patients with MAGE-A3-positive surgically resected NSCLC. Based on our results, further development of the MAGE-A3 immunotherapeutic for use in NSCLC has been stopped. Funding GlaxoSmithKline Biologicals SA.

Karcinom plic zaujima předni mista jak v incidenci, tak v mortalitě nadorových onemocněni celosvětově i v Ceske republice. V poslednich letech zaznamenala lecba NSCLC prudký rozvoj. Již v době stanoveni diagnozy je snahou co nejpřesněji urcit morfologickou diagnozu a pokud je to indikovano, provest geneticke testovani. Toto plati předevsim o nedlaždicobuněcných NSCLC. V roce 2013 byla publikovana ucinnost a bezpecnost pokracovaci udržovaci lecby (continuation maintenace) monoterapii pemetrexedem a diky pozitivnimu výsledku je tato lecba možna od května 2013 v Ceske republice. V nasi praci prezentujeme soubor 134 hodnocených pacientů, kteři absolvovali výse uvedenou lecbu. V realne klinicke praxi v Ceske republice bylo dosaženo lecbou pemetrexedem v pokracovaci udržovaci lecbě lepsich výsledků než v registracni studii a lecba byla velmi dobře snasena. Zatim median celkoveho přežiti (OS) byl stanoven na 23,5 měsice.

Celosvětově představuje bronchogenni karcinom jednu z nejcastějsich malignit. V průměru je každý rok diagnostikovano 1,8 milionu nových připadů rakoviny plic a asi 1,6 milionu pacientů na plicni karcinom zemře. Kurativni lecba je možna pouze u casných stadii nemoci, ktera ale v praxi představuji asi pětinu nových diagnoz. Převažna větsina nemocných je diagnostikovana s pokrocilou chorobou a jsou leceni s paliativnim umyslem. Hlavni lecebnou modalitou je systemova lecba, event. radioterapie. Imunoterapie je lecebnou možnosti, ktera pro boj s nadorem využiva schopnosti vlastniho imunitniho systemu. Tato lecebna modalita prodělala v poslednich letech pozoruhodný pokrok a od roku 2015 se stala soucasti lecebných doporuceni.

Background CASPIAN is a phase 3, open-label study of 1L platinum-etoposide (EP) ± durvalumab (D) ± tremelimumab (T) for pts with ES-SCLC. D+EP significantly improved OS vs EP alone (HR 0.73 [95% CI 0.59–0.91]; p = 0.0047) at a planned interim analysis. Rates of all-cause AEs and AEs leading to discontinuation were similar between arms. Immune-mediated AEs (imAEs) were higher with D+EP vs EP, while numerically fewer pts in the D+EP arm had serious AEs (SAEs; 30.9 vs 36.1%). Here we present further safety, PK and immunogenicity results. Methods Treatment-naive pts with ES-SCLC were randomised 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. Investigator’s choice of carboplatin or cisplatin was allowed. In the IO arms, pts received 4 cycles of EP, followed by D 1500 mg q4w until progression; up to 6 cycles of EP and optional PCI were permitted in the control arm. Safety, PK and immunogenicity were secondary endpoints. Results 265 pts received D+EP and 266 received EP. Serum concentrations were within the expected range for D and were similar across both arms for EP. Of 201 anti-drug antibody (ADA)-evaluable pts in the D+EP arm, 11 (5.5%) were +ve for ADA to D at baseline only; no pts were +ve for treatment-emergent ADA or neutralising antibodies. The most common AEs, grade 3/4 AEs and SAEs in both arms were haematological toxicities. These were well managed using standard therapies per local practice; colony stimulating factor use was 50.4% in the D+EP arm and 56.9% in the EP arm, and 12.7% and 20.8% received blood transfusions. When events that coincided with cycles 5 and 6 of EP in the control arm were removed, the overall SAE rate was similar between arms (30.9% for D+EP vs 30.1% for EP). Most imAEs were low grade, endocrine-related and managed with corticosteroid or endocrine therapy; median time to onset was generally >60 days (table). Table . LBA2 D+EP (n = 265) EP (n = 266) imAE (group term) * Any grade, n (%) Grade ≥3, n (%) Median time to onset, † days (range) Any grade, n (%) Grade ≥3, n (%) Median time to onset, † days (range) Any imAE 52 (20) 13 (5) – 7 (3) 2 (1) – Hypothyroid 24 (9) 0 141 (42–283) 2 (1) 0 63 (62–64) Hyperthyroid 14 (5) 0 85.5 (22–372) 0 0 – Pneumonitis 7 (3) 2 (1) 191 (80–365) 2 (1) 2 (1) 177 (141–213) Hepatic 7 (3) 6 (2) 93 (31–256) 0 0 – Dermatitis/rash 4 (2) 0 33.5 (16–91) 2 (1) 0 31 (27–35) Diarrhoea/colitis 4 (2) 1 (0.4) 28 (9–114) 1 (0.4) 0 64 (64–64) Thyroiditis 4 (2) 0 144 (43–260) 0 0 – Type 1 diabetes 4 (2) 4 (2) 104 (38–316) 0 0 – * imAEs with incidence ≥2% in either arm are shown. † Time from first dose to onset of any grade imAEs. Conclusion In CASPIAN, the incidence of ADA to D was low and the safety profile of D+EP was consistent with previous reports of both D and EP. Clinical trial identification NCT03043872 (release date: February 6, 2017). Editorial acknowledgement Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Craig Turner, MSc, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study AstraZeneca PLC. Funding AstraZeneca. Disclosure M. Ozguroglu: Advisory / Consultancy, Advisory board participation: Janssen / Sanofi / Astellas; Honoraria (self): Novartis / Roche / Janssen / Sanofi / Astellas; Travel / Accommodation / Expenses: Bristol-Myers Squibb / Janssen. J.W. Goldman: Advisory / Consultancy: AstraZeneca / Genentech / Lilly; Research grant / Funding (self): AstraZeneca/MedImmune / Eli Lilly / Genentech / Bristol-Myers Squibb / Array BioPharma / Celgene / AbbVie; Speaker Bureau / Expert testimony: Merck. N. Reinmuth: Travel / Accommodation / Expenses, Personal fees and non-financial support: AstraZeneca / Boehringer-Ingelheim / Hoffmann La-Roche / Bristol-Myers Squibb / Pfizer; Non-remunerated activity/ies, Non-financial support: Abbvie; Travel / Accommodation / Expenses, Personal fees: MSD Sharp & Dohme / Takeda. Y. Chen: Research grant / Funding (self): AstraZeneca / ISPEN / Roche / Bristol-Myers Squibb; Travel / Accommodation / Expenses, Personal fees: AstraZeneca / Genentech / Bristol-Myers Squibb / Merck / Novartis / Takeda / Eli Lilly / Guardant Health / Pfizer / Array Biopharma. K. Hotta: Research grant / Funding (self), Grants and personal fees: AstraZeneca / Lilly / Bristol-Myers Squibb; Travel / Accommodation / Expenses, Personal fees: MSD / Ono / Nipponkayaku / Taiho / Boehringer-Ingelheim / Chugai. F. Verderame: Research grant / Funding (self): AstraZeneca. M. Thomas: Full / Part-time employment: AstraZeneca. Y. Zheng: Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: AstraZeneca. A. Lloyd: Full / Part-time employment: AstraZeneca. H. Jiang: Full / Part-time employment: AstraZeneca; Shareholder / Stockholder / Stock options: AstraZeneca. L. Paz-Ares: Leadership role, Myself: Genomica; Leadership role, Immediate family member: European Medicines Agency; Honoraria (self), Myself: Roche/Genentech, Lilly, Pfizer, Boehringer-Ingelheim, Bristol-Myers Squibb, MSD, AstraZeneca, Merck Serono, PharmaMar, Novartis, Celgene, Sysmex, Amgen, Incyte; Travel / Accommodation / Expenses, Myself: Roche, AstraZeneca, AstraZeneca Spain, Merck, MSD, Bristol-Myers Squibb, Lilly, Pfizer; Spouse / Financial dependant, Other relationship [immediate family member]: Novartis, Ipsen, Pfizer, Servier, Sanofi, Roche, Amgen, Merck. All other authors have declared no conflicts of interest.

BACKGROUND Patients with advanced squamous-cell non-small-cell lung cancer (NSCLC) who have disease progression during or after first-line chemotherapy have limited treatment options. This randomized, open-label, international, phase 3 study evaluated the efficacy and safety of nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, as compared with docetaxel in this patient population. METHODS We randomly assigned 272 patients to receive nivolumab, at a dose of 3 mg per kilogram of body weight every 2 weeks, or docetaxel, at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. RESULTS The median overall survival was 9.2 months (95% confidence interval [CI], 7.3 to 13.3) with nivolumab versus 6.0 months (95% CI, 5.1 to 7.3) with docetaxel. The risk of death was 41% lower with nivolumab than with docetaxel (hazard ratio, 0.59; 95% CI, 0.44 to 0.79; P

Erlotinib is an epidermal growth factor receptor tyrosine-kinase inhibitor. Clinical trials have shown its efficacy in advanced non-small cell lung cancer (NSCLC). We conducted a large retrospective study based on clinical experience aiming to prove erlotinib’s efficacy and safety in patients with advanced-stage squamous cell NSCLC. Totally 375 patients with advanced-stage (IIIB, IV) squamous cell NSCLC were treated with erlotinib. Erlotinib was continued until disease progression or intolerable toxicity. 1 (0.3%) complete response (CR), 28 (7.5%) partial responses (PR) and 198 (52.8%) stable diseases (SD) were achieved. Overall response rate (ORR) and disease control rate (DCR) were 7.8% and 60.5%, respectively. Median progression-free survival (PFS) was 3.0 months and median overall survival (OS) was 7.6 months. PFS of patients with CR/PR, SD and PD were 7.6, 3.9 and 1.0 months, respectively (P

Background Platinum chemotherapy (carboplatin or cisplatin) + etoposide is the current 1L standard of care treatment (tx) for ES-SCLC. Despite high response rates on this regimen, patient (pt) outcomes remain poor. IMpower133 is a Ph1/3, double-blind, randomized, placebo (PBO)-controlled trial that is evaluating the efficacy and safety of adding PD-L1-inhibitor atezo or PBO to 1L tx for ES-SCLC (NCT02763579). Methods IMpower133 enrolled pts without prior tx for ES-SCLC; PD-L1 testing was not required. Pts were randomized 1:1 to four 21-day cycles of carboplatin (AUC 5 mg/mL/min IV, Day 1) + etoposide (100 mg/m2 IV, Days 1-3) with either atezo (1200 mg IV, Day 1) or PBO, then maintenance atezo or PBO until PD, unacceptable toxicity or loss of clinical benefit. Maintenance prophylactic cranial irradiation (PCI) was allowed per protocol, while definitive thoracic radiation (TR) was not. Coprimary endpoints were OS and investigator-assessed PFS. A key exploratory endpoint was outcomes by blood tumor mutation burden (bTMB) analyzed at prespecified cutoffs (≥ 16 vs < 16 and ≥ 10 vs < 10 mutations/Mb). Results Adding atezo to carboplatin + etoposide demonstrated significant improvement in efficacy (OS and PFS) in 1L ES-SCLC (Table). Survival benefits were consistent across key subgroups and prespecified bTMB cutoffs. 44 pts (22 in each arm [per ITT]) received PCI, and 7 (3 in atezo arm, 4 in PBO arm) received TR. Gr 3-4 tx-related adverse events (AEs) occurred in 57% of atezo pts vs 56% of PBO pts; serious tx-related AEs occurred in 23% vs 19%. Occurrence of CNS-related AEs in pts who had PCI are shown in the Table. Conclusion Adding atezo to carboplatin + etoposide resulted in a significant improvement in survival in this 1L ES-SCLC all-comers population. There were no new safety signals, including in pts who received PCI or TR. Atezo + carboplatin + etoposide may represent a new standard regimen for untreated ES-SCLC. Atezo + carboplatin + etoposiden = 201PBO + carboplatin + etoposiden = 202Co-primary endpointsMedian OS, mo12.310.3HR 0.70 (95% CI: 0.54, 0.91); P = 0.0069Median PFS, mo5.24.3HR 0.77 (95% CI: 0.62, 0.96) P = 0.017Secondary efficacy endpointsInvestigator-assessed confirmed ORR, %60.264.4Median DoR, mo4.23.9CNS-related AEs in pts who had PCI, n (%)a,bn = 23n = 21Headache8 (34.8)4 (19.0)Asthenia5 (21.7)2 (9.5)Dizziness2 (8.7)0Insomnia2 (8.7)1 (4.8)Fall2 (8.7)1 (4.8)aSafety population; safety analyses conducted according to tx received (1 pt randomized to the control arm received a dose of atezo).bIncludes AEs occurring in ≥ 2 patients. Citation Format: Aaron S. Mansfield, Stephen V. Liu, Aleksandra Szczęsna, Libor Havel, Maciej Kzrakowski, Maximilian J. Hochmair, Florian Huemer, György Losonczy, Melissa L. Johnson, Makoto Nishio, Martin Reck, Tony S. Mok, Sivuonthanh Lam, David S. Shames, Juan Liu, Fairooz Kabbinavar, Alan Sandler, Leora Horn. IMpower133: Primary efficacy and safety + CNS-related adverse events in a Ph1/3 study of first-line (1L) atezolizumab (atezo) + carboplatin + etoposide in extensive-stage SCLC (ES-SCLC) [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT199.

Lung cancer is the most common cancer in the world. Lung cancer is also the most common cause of death caused by cancer worldwide with fatality rate (the overall ratio of mortality to incidence) of 0.87. Nowadays, cure can be achieved only in early disease stages using surgical resection or radical radiotherapy. This approach can be considered only in 20% of patients. Outcome of therapy of loco-regionally advanced or metastatic lung cancer are unsatisfactory. Despite improvement of radiotherapy techniques, despite introduction of new cytostatics and new targeted therapies, long-term disease control could be achieved only in minority of patients. Immunotherapy is a therapeutic approach which uses the immune system itself against cancer. This article is a summary of the authors 17-year experience with different immunotherapeutic agents. It will be focused on big anti-cancer vaccines trials START and MAGRIT, and especially trials in the upcoming era of checkpoint inhibitors. Future perspectives of immunotherapy and its combination of recent therapeutic approaches will be considered.

Characteristics of NSCLC Patients Treated in First Line Treatment with Tyrosine Kinase Inhibitors (TKI) - Real Data from the Czech Republic.

Aim: Adjuvant chemotherapy (ACT) is the standard of care for Stage II and IIIA NSCLC, and for high risk Stage IB NSCLC. However, the 5-year disease-free survival remains poor (35-50%) and about half of the patients will not receive ACT for various reasons. This Phase III trial investigated whether the recMAGE-A3 + AS15 cancer immunotherapeutic (MAGE-A3 CI) as adjuvant therapy improved disease-free survival (DFS) in patients with resected NSCLC. Methods: MAGRIT was a randomized, double-blind, placebo-controlled trial in patients with completely resected MAGE-A3-positive NSCLC Stages IB, II, and IIIA (TNM version 6) and who did or did not receive ACT. Patients were randomly assigned (2:1) to receive 13 intramuscular injections of MAGE-A3 CI or placebo over a 27-month (m) treatment period. The three co-primary endpoints were DFS in the overall and in the no-ACT population and DFS in patients with a potentially predictive gene signature (GS). Results: Out of 13,849 patients screened, 4,210 patients had a MAGE-A3 positive tumour sample and 2,272 patients were randomised and treated. Overall, 52% of the patients received ACT; 47%, 36% and 17% were Stage IB, II and IIIA, respectively. Median age was 63 years and 24% of patients were females. Mean relative dose intensity was above 98% in both groups throughout the treatment period. Median follow-up at the time of final analysis was 38.8m. Median DFS was 60.5m and 57.9m respectively for MAGE-A3 CI and placebo (HR 1.024, 95% CI 0.891-1.177; p = 0.7379). In patients who did not receive ACT, median DFS was 58.0m and 56.9m for MAGE-A3 CI and placebo groups, respectively (HR 0.970, 95% CI 0.797-1.179; p = 0.7572). The rate of grade ≥ 3 adverse events (16%) did not differ between treatment groups. Conclusions: Treatment of NSCLC patients with MAGE-A3 CI did not increase DFS compared to placebo in either the overall population or in patients who did not receive ACT. Due to the absence of treatment effect, a GS predictive of clinical benefit to MAGE-A3 CI could not be identified. Funding Source: GlaxoSmithKline Biologicals SA. Disclosure: J.F. Vansteenkiste: Pr Vansteenkiste received GSK fees as Primary investigator for the MAGRIT study; B. Cho: Dr Cho received consultancy fees from Novartis and Boehringer-ingelheim; T. De Pas: No conflicts of interest. Fee received from GSK as member of steering committee of the study; J. Jassem: Dr Jassem received grant and personal fees for Consultancy from GSK; M. Yoshimura: Pr Yoshimura received GSK fees as Primary investigator for the MAGRIT and PEARL study; H. Nakayama: Dr Nakayama received GSK fees as Primary investigator for the MAGRIT and PEARL study; T. Mitsudomi: Dr Mitsudomi received personal fees from GSK for an advisory role; B. Spiessens: Bart Spiessens is employee of GSK and do own stock options of GSK; V. Brichard: Dr Birchart is GSK employee and do own Stock options from GSK; C. Debruyne: Dr Debruyne is GSK employee and do own GSK stock options; P. Therasse: GSK employee and Stock options owner; N. Altorki: Dr Altorki received GSK fees for trial conduct of GSK studies. All other authors have declared no conflicts of interest.

Background Individualized treatments in NSCLC are now based on molecular and/or histological data. This randomized trial (2/1) was set up to assess the efficacy of NC compared to PC for pts with nSCC. The primary end-point was disease control rate (DCR) including overall response rate (ORR) and stable disease (SD). Methods Pts received N60-80 mg/m2 D1, D8 + C80 mg/m2 D1 or P500 mg/m2 + C75 mg/m2 D1 for 4 cycles q3w; pts with DCR received single agent continuation maintenance (CM) until progression or toxicity. Results From 10/09 to 02/11, 151 pts were treated with NC or PC. ITT = 151 NC n = 100 PC n = 51 Male/Stage IV (%) 62.0/87.0 64.7/88.2 Median age (y, range) 61.0 (38.4-75.1) 63.8 (40.3-75.5) Combination: (%) ITT(95% CI) DCR 75.0 (65.3-83.1) 74.5 (60.4-85.7) ORR 21.0 (13.5-30.3) 23.5 (12.8-37.5) Combination + CM:(%) ITT (95% CI) n= 53 n = 33 DCR 75 (65.3-83.1) 76.5 (62.5-87.2) ORR 24 (16.0-33.6) 31.4 (19.1-45.9) Median PFS ITT (m,range) 4.2 (3.6-4.7) 4.2 (3.2-5.6) PFS ITT at 6/12/18m (%) 33.0/10.3/5.5 27.5/7.4/2.5 Median OS ITT (m,range) 10.6 (7.8-12.1) 10.8 (7.0-14.5) Related toxicities G3/4 (%pts) NC/PC during Combination: anemia 9.0(G3)/8.2, leucopenia 26.0/10.2, neutropenia 44.0/18.3, febrile neutro 2.0/2.0, thrombocytopenia 0/6.1, fatigue(G3) 7.0/3.9, hyperglycemia 4.0/7.8, nausea(G3) 5.0/0, vomiting(G3) 7.0/2.0, stomatitis(G3) 0/2.0, pneumonia(G3) 0/2.0, deep vein thrombosis(G3) 0/2.0, pulmonary embolism(G4) 0/2.0. During Maintenance: anemia 5.0/4.1, leucopenia 2.0/10.2, neutropenia 11.0/20.4, febrile neutro 3.8/0, fatigue (G3) 3.8/0, stomatitis(G3) 1.9/ 3.0, pain 3.8/6.0, Respiratory disorders 0/4.0, deep vein thrombosis (G3)0/2.0. Deaths potentially related to CT 2/1. Conclusions NC and PC had similar efficacy. In the present economic context, the acquisition cost of the two platinum based doublets should be considered in the treatment decision making of pts with advanced nSCC NSCLC. Disclosure S. Malasse: Statistician of the study Employment for the sponsor. F. Biville-Hedouin: Medical Project Manager of the study Employment for the sponsor. All other authors have declared no conflicts of interest.