Search

Pembrolizumab is a standard-of-care for advanced non-small-cell lung cancer (NSCLC). We assessed pembrolizumab as adjuvant therapy for completely resected stage IB-IIIA NSCLC.In this randomised, triple-blind, phase 3 trial (PEARLS/KEYNOTE-091), patients were recruited from 196 medical centres in 29 countries. Eligible patients were aged 18 years or older, with completely resected, pathologically confirmed stage IB (tumours of ≥4 cm in diameter), II, or IIIA NSCLC per the American Joint Committee on Cancer staging system (7th edition) of any histology or PD-L1 expression level, and an Eastern Cooperative Oncology Group performance status of 0 or 1; adjuvant chemotherapy was to be considered for stage IB disease and was strongly recommended for stage II and IIIA disease, according to national and local guidelines. Using a central interactive voice-response system, eligible participants were randomly assigned (1:1), using a minimisation technique and stratified by disease stage, previous adjuvant chemotherapy, PD-L1 expression, and geographical region, to pembrolizumab 200 mg or placebo, both administered intravenously every 3 weeks for up to 18 cycles. Participants, investigators, and analysts were masked to treatment assignment. Dual primary endpoints were disease-free survival in the overall population and in the population with PD-L1 tumour proportion score (TPS) of 50% or greater. Efficacy was assessed in the intention-to-treat (ITT) population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants randomly assigned to treatment who received at least one dose of study treatment. Here we report results of the second interim analysis, prespecified to occur when approximately 118 disease-free survival events had occurred in the PD-L1 TPS of 50% or greater population. This study is registered with ClinicalTrials.gov, NCT02504372, and is active but not recruiting.Between Jan 20, 2016, and May 6, 2020, 1177 (60%) of 1955 screened participants were randomly assigned to pembrolizumab (n=590, including n=168 with PD-L1 TPS of ≥50%) or placebo (n=587; including n=165 with PD-L1 TPS of ≥50%) and included in the ITT population. Median follow-up as of data cutoff (Sept 20, 2021) for this interim analysis was 35·6 months (IQR 27·1-45·5). In the overall population, median disease-free survival was 53·6 months (95% CI 39·2 to not reached) in the pembrolizumab group versus 42·0 months (31·3 to not reached) in the placebo group (HR 0·76 [95% CI 0·63-0·91], p=0·0014). In the PD-L1 TPS of 50% or greater population, median disease-free survival was not reached in either the pembrolizumab group (95% CI 44·3 to not reached) or the placebo group (95% CI 35·8 to not reached; HR 0·82 [95% CI 0·57-1·18]; p=0·14). Grade 3 or worse adverse events occurred in 198 (34%) of 580 participants who received pembrolizumab and 150 (26%) of 581 participants who received placebo. Grade 3 or worse events that occurred in at least ten participants in either treatment group were hypertension (35 [6%]) and pneumonia (12 [2%]) with pembrolizumab and hypertension (32 [6%]) with placebo. Serious adverse events occurred in 142 (24%) participants in the pembrolizumab group and 90 (15%) in the placebo group; serious adverse events that occurred in more than 1% of participants were pneumonia (13 [2%]), pneumonitis (12 [2%]), and diarrhoea (seven [1%]) with pembrolizumab and pneumonia (nine [2%]) with placebo. Treatment-related adverse events led to death in four (1%) participants treated with pembrolizumab (one due to both cardiogenic shock and myocarditis, one due to both septic shock and myocarditis, one due to pneumonia, and one due to sudden death) and in no participants treated with placebo.Pembrolizumab significantly improved disease-free survival compared with placebo and was not associated with new safety signals in completely resected, PD-L1-unselected, stage IB-IIIA NSCLC. Pembrolizumab is potentially a new treatment option for stage IB-IIIA NSCLC after complete resection and, when recommended, adjuvant chemotherapy, regardless of PD-L1 expression.Merck Sharpamp; Dohme, a subsidiary of Merckamp; Co.

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/aim LUCAS is a clinical lung cancer registry (ClinicalTrials.gov identifier is NCT04228237), prospectively collecting data from newly diagnosed lung cancer patients in seven pneumooncology centers in the Czech Republic, since June 1, 2018. The aim of the study was to assess the stage of the disease at the time of diagnosis, percentage of morphological types, survival, percentage of driving mutations, eligibility for radical surgery, and percentage of patients who undergo radical surgery, in the non-smoking population in comparison with smokers and former smokers. Patients and methods The total number of patients in the registry at the time of the analysis was 2,743. Only 2,439 patients with complete records (smoking status, stage, and type of tumor) were included in this study. Results The analysis indicated that non-smokers are diagnosed at a later stage of the disease but they have a better survival rate than smokers. Fewer smokers with stage III disease who are eligible for radical surgery will undergo surgery compared to non-smokers with the same clinical stage. Driving mutations are more common in non-smokers, even after adjustment for the more frequent occurrence of adenocarcinoma in the group of non-smokers. Conclusion The data from LUCAS registry are consistent with already known facts, suggesting that the LUCAS registry is a useful clinical tool.

Background: First-line durvalumab plus etoposide with either cisplatin or carboplatin (platinum–etoposide) showed a significant improvement in overall survival versus platinum–etoposide alone in patients with extensive-stage small-cell lung cancer (ES-SCLC) in the CASPIAN study. Here we report updated results, including the primary analysis for overall survival with durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide alone. Methods: CASPIAN is an ongoing, open-label, sponsor-blind, randomised, controlled phase 3 trial at 209 cancer treatment centres in 23 countries worldwide. Eligible patients were aged 18 years or older (20 years in Japan) and had treatment-naive, histologically or cytologically documented ES-SCLC, with a WHO performance status of 0 or 1. Patients were randomly assigned (1:1:1) in blocks of six, stratified by planned platinum, using an interactive voice-response or web-response system to receive intravenous durvalumab plus tremelimumab plus platinum–etoposide, durvalumab plus platinum–etoposide, or platinum–etoposide alone. In all groups, patients received etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL/min or cisplatin 75–80 mg/m2 on day 1 of each cycle. Patients in the platinum–etoposide group received up to six cycles of platinum–etoposide every 3 weeks and optional prophylactic cranial irradiation (investigator's discretion). Patients in the immunotherapy groups received four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks. The two primary endpoints were overall survival for durvalumab plus platinum–etoposide versus platinum–etoposide and for durvalumab plus tremelimumab plus platinum–etoposide versus platinum–etoposide in the intention-to-treat population. Safety was assessed in all patients who received at least one dose of study treatment. This study is registered at ClinicalTrials.gov, NCT03043872. Findings: Between March 27, 2017, and May 29, 2018, 972 patients were screened and 805 were randomly assigned (268 to durvalumab plus tremelimumab plus platinum–etoposide, 268 to durvalumab plus platinum–etoposide, and 269 to platinum–etoposide). As of Jan 27, 2020, the median follow-up was 25·1 months (IQR 22·3–27·9). Durvalumab plus tremelimumab plus platinum–etoposide was not associated with a significant improvement in overall survival versus platinum–etoposide (hazard ratio [HR] 0·82 [95% CI 0·68–1·00]; p=0·045); median overall survival was 10·4 months (95% CI 9·6–12·0) versus 10·5 months (9·3–11·2). Durvalumab plus platinum–etoposide showed sustained improvement in overall survival versus platinum–etoposide (HR 0·75 [95% CI 0·62–0·91]; nominal p=0·0032); median overall survival was 12·9 months (95% CI 11·3–14·7) versus 10·5 months (9·3–11·2). The most common any-cause grade 3 or worse adverse events were neutropenia (85 [32%] of 266 patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 64 [24%] of 265 patients in the durvalumab plus platinum–etoposide group, and 88 [33%] of 266 patients in the platinum–etoposide group) and anaemia (34 [13%], 24 [9%], and 48 [18%]). Any-cause serious adverse events were reported in 121 (45%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group, 85 (32%) in the durvalumab plus platinum–etoposide group, and 97 (36%) in the platinum–etoposide group. Treatment-related deaths occurred in 12 (5%) patients in the durvalumab plus tremelimumab plus platinum–etoposide group (death, febrile neutropenia, and pulmonary embolism [n=2 each]; enterocolitis, general physical health deterioration and multiple organ dysfunction syndrome, pneumonia, pneumonitis and hepatitis, respiratory failure, and sudden death [n=1 each]), six (2%) patients in the durvalumab plus platinum–etoposide group (cardiac arrest, dehydration, hepatotoxicity, interstitial lung disease, pancytopenia, and sepsis [n=1 each]), and two (1%) in the platinum–etoposide group (pancytopenia and thrombocytopenia [n=1 each]). Interpretation: First-line durvalumab plus platinum–etoposide showed sustained overall survival improvement versus platinum–etoposide but the addition of tremelimumab to durvalumab plus platinum–etoposide did not significantly improve outcomes versus platinum–etoposide. These results support the use of durvalumab plus platinum–etoposide as a new standard of care for the first-line treatment of ES-SCLC. Funding: AstraZeneca.

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.

Background: Most patients with small-cell lung cancer (SCLC) have extensive-stage disease at presentation, and prognosis remains poor. Recently, immunotherapy has demonstrated clinical activity in extensive-stage SCLC (ES-SCLC). The CASPIAN trial assessed durvalumab, with or without tremelimumab, in combination with etoposide plus either cisplatin or carboplatin (platinum–etoposide) in treatment-naive patients with ES-SCLC. Methods: This randomised, open-label, phase 3 trial was done at 209 sites across 23 countries. Eligible patients were adults with untreated ES-SCLC, with WHO performance status 0 or 1 and measurable disease as per Response Evaluation Criteria in Solid Tumors, version 1.1. Patients were randomly assigned (in a 1:1:1 ratio) to durvalumab plus platinum–etoposide; durvalumab plus tremelimumab plus platinum–etoposide; or platinum–etoposide alone. All drugs were administered intravenously. Platinum–etoposide consisted of etoposide 80–100 mg/m2 on days 1–3 of each cycle with investigator's choice of either carboplatin area under the curve 5–6 mg/mL per min or cisplatin 75–80 mg/m2 (administered on day 1 of each cycle). Patients received up to four cycles of platinum–etoposide plus durvalumab 1500 mg with or without tremelimumab 75 mg every 3 weeks followed by maintenance durvalumab 1500 mg every 4 weeks in the immunotherapy groups and up to six cycles of platinum–etoposide every 3 weeks plus prophylactic cranial irradiation (investigator's discretion) in the platinum–etoposide group. The primary endpoint was overall survival in the intention-to-treat population. We report results for the durvalumab plus platinum–etoposide group versus the platinum–etoposide group from a planned interim analysis. Safety was assessed in all patients who received at least one dose of their assigned study treatment. This study is registered at ClinicalTrials.gov, NCT03043872, and is ongoing. Findings: Patients were enrolled between March 27, 2017, and May 29, 2018. 268 patients were allocated to the durvalumab plus platinum–etoposide group and 269 to the platinum–etoposide group. Durvalumab plus platinum–etoposide was associated with a significant improvement in overall survival, with a hazard ratio of 0·73 (95% CI 0·59–0·91; p=0·0047]); median overall survival was 13·0 months (95% CI 11·5–14·8) in the durvalumab plus platinum–etoposide group versus 10·3 months (9·3–11·2) in the platinum–etoposide group, with 34% (26·9–41·0) versus 25% (18·4–31·6) of patients alive at 18 months. Any-cause adverse events of grade 3 or 4 occurred in 163 (62%) of 265 treated patients in the durvalumab plus platinum–etoposide group and 166 (62%) of 266 in the platinum–etoposide group; adverse events leading to death occurred in 13 (5%) and 15 (6%) patients. Interpretation: First-line durvalumab plus platinum–etoposide significantly improved overall survival in patients with ES-SCLC versus a clinically relevant control group. Safety findings were consistent with the known safety profiles of all drugs received. Funding: AstraZeneca.

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 First-line pembrolizumab monotherapy improves overall and progression-free survival in patients with untreated metastatic non-small-cell lung cancer with a programmed death ligand 1 (PD-L1) tumour proportion score (TPS) of 50% or greater. We investigated overall survival after treatment with pembrolizumab monotherapy in patients with a PD-L1 TPS of 1% or greater. Methods This randomised, open-label, phase 3 study was done in 213 medical centres in 32 countries. Eligible patients were adults (≥18 years) with previously untreated locally advanced or metastatic non-small-cell lung cancer without a sensitising EGFR mutation or ALK translocation and with an Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1, life expectancy 3 months or longer, and a PD-L1 TPS of 1% or greater. Randomisation was computer generated, accessed via an interactive voice-response and integrated web-response system, and stratified by region of enrolment (east Asia vs rest of world), ECOG performance status score (0 vs 1), histology (squamous vs non-squamous), and PD-L1 TPS (≥50% vs 1-49%). Enrolled patients were randomly assigned 1:1 in blocks of four per stratum to receive pembrolizumab 200 mg every 3 weeks for up to 35 cycles or the investigator's choice of platinum-based chemotherapy for four to six cycles. Primary endpoints were overall survival in patients with a TPS of 50% or greater, 20% or greater, and 1% or greater (one-sided significance thresholds, p=0·0122, p=0·0120, and p=0·0124, respectively) in the intention-to-treat population, assessed sequentially if the previous findings were significant. This study is registered at ClinicalTrials.gov, number NCT02220894. Findings From Dec 19, 2014, to March 6, 2017, 1274 patients (902 men, 372 women, median age 63 years [IQR 57-69]) with a PD-L1 TPS of 1% or greater were allocated to pembrolizumab (n=637) or chemotherapy (n=637) and included in the intention-to-treat population. 599 (47%) had a TPS of 50% or greater and 818 patients (64%) had a TPS of 20% or greater. As of Feb 26, 2018, median follow-up was 12·8 months. Overall survival was significantly longer in the pembrolizumab group than in the chemotherapy group in all three TPS populations (≥50% hazard ratio 0·69, 95% CI 0·56-0·85, p=0·0003; ≥20% 0·77, 0·64-0·92, p=0·0020, and ≥1% 0·81, 0·71-0·93, p=0·0018). The median surival values by TPS population were 20·0 months (95% CI 15·4-24·9) for pembrolizumab versus 12·2 months (10·4-14·2) for chemotherapy, 17·7 months (15·3-22·1) versus 13·0 months (11·6-15·3), and 16·7 months (13·9-19·7) versus 12·1 months (11·3-13·3), respectively. Treatment-related adverse events of grade 3 or worse occurred in 113 (18%) of 636 treated patients in the pembrolizumab group and in 252 (41%) of 615 in the chemotherapy group and led to death in 13 (2%) and 14 (2%) patients, respectively. Interpretation The benefit-to-risk profile suggests that pembrolizumab monotherapy can be extended as first-line therapy to patients with locally advanced or metastatic non-small-cell lung cancer without sensitising EGFR or ALK alterations and with low PD-L1 TPS. Funding Merck Sharp & Dohme.

8512 Background: At the second interim analysis (IA2) of the triple-blind, phase 3 PEARLS/KEYNOTE-091 study (NCT02504372), pembrolizumab significantly improved DFS compared with placebo in patients (pts) with completely resected stage IB (T ≥4 cm) to IIIA NSCLC per AJCC v7, regardless of PD-L1 expression (N = 1177, HR 0.76, 95% CI 0.63-0.91, P = 0.0014). We present DFS in subgroups related to surgery, disease burden, and adjuvant chemotherapy use. Methods: Pts had pathologically confirmed, completely resected stage IB (T ≥4 cm) to IIIA NSCLC of any PD-L1 expression and ECOG PS 0-1. Systematic complete or lobe-specific mediastinal lymph node dissection was recommended; minimally, the subcarinal and 1 lobe-specific lymph node must have been examined. Adjuvant chemotherapy of ≤4 cycles was given as indicated by local guidelines. Eligible pts were randomized 1:1 to pembrolizumab 200 mg or placebo Q3W for 18 doses (̃1 y). Treatment effects on DFS were assessed in prespecified subgroups of with and without adjuvant chemotherapy and in exploratory subgroups defined by surgery type, pN stage, tumor size, no. of adjuvant chemotherapy cycles, and adjuvant regimen; only subgroups of > 50 pts were analyzed. Data cutoff for IA2 was September 20, 2021 (median time from randomization to cutoff, 35.6 mo). Results: By surgery type, the HR (95% CI) for DFS was 0.78 (0.64-0.96) for lobectomy (n = 925), 0.85 (0.43-1.69) for bilobectomy (n = 92), and 0.71 (0.40-1.24) for pneumonectomy (n = 127). For subgroups based on nodal status, HR (95% CI) for DFS was 0.63 (0.46-0.86) for pN0 (n = 490), 0.77 (0.57-1.03) for pN1 (n = 456), and 1.00 (0.71-1.41) for pN2 (n = 231). By tumor size, and irrespective of nodal status, the HR (95% CI) for DFS was 0.91 (0.69-1.20) for size ≤4 cm (n = 491) and 0.70 (0.55-0.89) for size > 4 cm (n = 685). The HR (95% CI) for DFS was 0.73 (0.60-0.89) in pts who received adjuvant chemotherapy (n = 1010) and 1.25 (0.76-2.05) in those who did not (n = 167). Among pts who received adjuvant chemotherapy, HR (95% CI) for DFS by number of cycles was 0.59 (0.28-1.26) for 1-2 (n = 67) and 0.74 (0.61-0.91) for 3-4 (n = 943); by regimen, it was 0.74 (0.55-0.98) for cisplatin + vinorelbine (n = 491), 0.51 (0.31-0.83) for carboplatin + vinorelbine (n = 151), 1.21 (0.73-1.98) for carboplatin + paclitaxel (n = 135), 0.65 (0.30-1.40) for cisplatin + gemcitabine (n = 57), and 0.68 (0.41-1.14) for other regimen (n = 176). Conclusions: Pembrolizumab generally improved DFS versus placebo regardless of type of surgery, lymph node involvement, tumor size, and type and extent of adjuvant chemotherapy in pts with completely resected stage IB (T ≥4 cm) to IIIA NSCLC. These data support the benefit of pembrolizumab as adjuvant therapy for early-stage NSCLC following complete resection and, if indicated, adjuvant chemotherapy. Clinical trial information: NCT02504372.

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.

9068 Background: In the Phase 3, randomized, open-label CASPIAN study, first-line durvalumab (D) added to etoposide plus either cisplatin or carboplatin (EP) significantly improved OS vs EP alone (HR 0.73 [95% CI 0.59–0.91]; p = 0.0047) in pts with ES-SCLC at the planned interim analysis. Here we describe treatment patterns and outcomes for pts according to brain metastases. Methods: Treatment-naïve pts (WHO PS 0/1) with ES-SCLC received 4 cycles of D 1500 mg + EP q3w followed by maintenance D 1500 mg q4w until disease progression (PD) or up to 6 cycles of EP q3w and optional prophylactic cranial irradiation (PCI; investigator’s discretion). Pts with either asymptomatic or treated and stable brain metastases were eligible. Brain imaging was suggested for pts with suspected brain metastases, but was not mandated at screening or during treatment. The primary endpoint was OS. Analysis of OS and PFS in pt subgroups with and without brain metastases was prespecified. Other analyses in these subgroups were post hoc. Data cutoff: Mar 11, 2019. Results: At baseline, 28 (10.4%) of 268 pts in the D + EP arm and 27 (10.0%) of 269 pts in the EP arm had known brain metastases; of these, only 3 pts (~11% of those with baseline brain metastases) in each arm received radiotherapy (RT) to the brain prior to study entry. D + EP consistently improved OS vs EP in pts with or without known brain metastases at baseline (HR 0.69 [95% CI 0.35–1.31] and 0.74 [0.59–0.93], respectively); PFS was also consistently improved with D + EP regardless of the presence or not of baseline brain metastases (HR 0.73 [0.42–1.29] and 0.78 [0.64–0.95]). Among pts without known brain metastases at baseline, similar proportions developed new brain metastases at first PD in the D + EP (20/240; 8.3%) and EP arms (23/242; 9.5%), despite 19 (7.9%) pts in the EP arm having received PCI. Overall, 48 of 268 (17.9%) and 49 of 269 (18.2%) pts in the D + EP and EP arms received RT to the brain subsequent to study treatment; rates remained similar across the D + EP and EP arms regardless of baseline brain metastases (11 of 28 [39.3%] and 11 of 27 [40.7%] pts with known baseline brain metastases, compared to 37 of 240 [15.4%] and 38 of 242 [15.7%] pts without known baseline brain metastases). Conclusions: In CASPIAN, OS and PFS outcomes were improved with D + EP vs EP regardless of baseline brain metastases, consistent with the ITT analyses. Rates of new brain metastases at first PD were similar between arms, although PCI was permitted only in the control arm. Rates of subsequent RT to the brain were also similar in both arms. Clinical trial information: NCT03043872.

9002 Background: CASPIAN is an open-label, Phase 3 study of durvalumab (D) ± tremelimumab (T) + etoposide and either cisplatin or carboplatin (EP) for pts with 1L ES-SCLC. At the planned interim analysis (data cutoff Mar 11, 2019; 63% maturity), D + EP demonstrated a statistically significant improvement in OS compared with EP alone (HR 0.73 [95% CI 0.59–0.91]; p=0.0047). Here we present a planned updated analysis of OS for D + EP vs EP and the first results for D + T + EP vs EP. Methods: Treatment-naïve pts with ES-SCLC (WHO PS 0/1) were randomized 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. In the IO arms, pts received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w until disease progression. Pts received one additional dose of T 75 mg post EP in the D + T + EP arm. In the EP arm, pts received up to 6 cycles of EP and optional PCI (investigator’s discretion). The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Results: 268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively; baseline characteristics were generally well balanced across arms. As of Jan 27, 2020, the median follow-up was 25.1 mo, 82% maturity. D + EP continued to demonstrate improvement in OS vs EP, with a HR of 0.75 (95% CI 0.62–0.91; nominal p=0.0032); median OS 12.9 vs 10.5 mo, respectively. 22.2% of pts were alive at 2 y with D + EP vs 14.4% of pts with EP. D + T + EP numerically improved OS vs EP, however this did not reach statistical significance per the prespecified statistical plan: HR 0.82 (95% CI 0.68–1.00; p=0.0451 [p≤0.0418 required for stat sig]); the median OS was 10.4 mo and 23.4% of pts were alive at 2 y. Secondary endpoints of PFS and ORR remained improved with D + EP vs EP and will be presented. Confirmed investigator-assessed ORR was similar for D + T + EP vs EP (58.4% vs 58.0%). Median PFS was similar for D + T + EP vs EP (4.9 mo vs 5.4 mo), but the 12-mo PFS rate was numerically higher (16.9% vs 5.3%); PFS HR 0.84 (95% CI 0.70–1.01). In the D + EP, D + T + EP and EP arms, respectively, incidences of all-cause AEs of Grade 3/4 were 62.3%, 70.3% and 62.8%; AEs leading to discontinuation 10.2%, 21.4% and 9.4%; and AEs leading to death 4.9%, 10.2% and 5.6%. Conclusions: The addition of durvalumab to EP continued to demonstrate improvement in OS compared with a robust control arm, further supporting this regimen as a new standard of care for 1L ES-SCLC offering the flexibility of platinum choice. No additional benefit was observed when T was combined with D + EP in this pt population. Safety findings in all arms remained consistent with the known safety profiles of all agents. Clinical trial information: NCT03043872.

Background and Aim: From October 2013 there is a possibility to treat patients with NSCLC and with activated epidermal growth factor receptor (EGFR) mutations with three TKI in the Czech Republic. We have tried to find differences among patient groups treated with single TKI in 1st line of treatment. Patients and methods: Only patients with EGFR mutation and in which 1st line treatment started in October 2013 until October 2017 were included in analysis. We analysed 347 patients (gefitinib - 164 patients, afatinib - 130 patients, erlotinib - 53 patients). Results: Between these three groups of patients there was no statistically significant difference in sex (p=0.988), in smoking habits (p=0.549), in type of EGFR mutation (p=0.200), in adenocarcinoma proportion (p=0.256). There was statistically significant difference according to age (p=0.001), PS ( Conclusion: We have not found any important difference in basic characteristic of patients treated in 1st line treatment with TKI (sex, smoking, histology and type of EGFR mutation) except for the age – patients treated with afatinib were younger. We have not found any important difference in response to treatment, in disease control and OS. We found a significant difference in PS segmentation, in occurrence of adverse events and PFS.

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

Background and Aim: From October 2013 there is a possibility to treat patients with NSCLC and with activated epidermal growth factor receptor (EGFR) mutations with three TKI (afatinib, eriotinib, gefitinib) in the Czech Republic. We have tried to find differences among patient groups treated with single TKI in 1st line of treatment. Patients and methods: As data source we used the TULUNG registry, which is focused on the data collection of patients with NSCLC treated with target therapy in the Czech Republic. We analysed 232 patients (gefitinib - 115 patients, afatinib - 77 patients, eriotinib - 40 patients.). Statistical significance was assessed using the Fisher's exact test or Kruskal-Wallis test (a=0.05).

Background The combination of oral vinorelbine plus cisplatin has been studied in numerous trials as first-line treatment of patients with non–small cell lung cancer (NSCLC) regardless of histologic subtype. NAVoTrial 01 is the first study that explores this combination specifically in nonsquamous (NS) NSCLC by assessing the feasibility of this doublet (ratio 1:2) in an investigational approach. A reference arm with pemetrexed plus cisplatin was included. Maintenance therapy with single-agent therapy after 4 cycles of combination therapy was included in the study schedules because it reflected a trend in first-line treatment of NSCLC. Patients and Methods Stage IIIB/IV untreated/relapsed patients with NS NSCLC received a 3-week cycle of pemetrexed 500 mg/m² and cisplatin 75 mg/m² on day 1 (arm A) or oral vinorelbine 80 mg/m² on days 1 and 8 (first cycle 60 mg/m²) and cisplatin 80 mg/m² on day 1 (arm B). After 4 cycles, patients without disease progression received single-agent maintenance treatment with pemetrexed or oral vinorelbine. Results Overall, 153 patients were randomized (arm A/arm B: 51/102). Disease control rate (%) for arm A was 76.5 (95% confidence interval [CI], 62.5-87.2) and for arm B it was 75.0 (95% CI, 65.3-83.1), Response rates for arm A were 31.4% (95% CI, 19.1-45.9) and for arm B were 24.0% (95% CI, 16.0-33.6). Median progression-free survival for arm A was 4.3 months (95% CI, 3.8-5.6) and for arm B it was 4.2 months (95% CI, 3.6-4.7). Median survival for arm A was 10.8 months (95% CI, 7.0-16.4) and for arm B it was 10.2 months (95% CI, 7.8-11.9). Main grade 3/4 hematologic toxicities were neutropenia 18.3% (arm A) and 44.0% (arm B), whereas febrile neutropenia was reported in 2% of patients in each arm. Conclusion Oral vinorelbine and cisplatin had an efficacy in line with that achieved with a standard treatment such as pemetrexed and cisplatin, coupled with an acceptable safety profile.

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.

9039 Background: Immunotherapy aiming the induction of tumor cell specific immune responses controlling the tumor growth, has emerged as a promising treatment modality in lung cancer(LuCa). Autologous DCVAC can present tumor antigens to elicit a durable immune response. We hypothesized that adding DCVAC to the standard of care chemotherapy (ct) could prolong overall survival (OS) and progression-free survival (PFS). Methods: This study evaluated the efficacy and safety of DCVAC/LuCa (active cellular immunotherapy based on dendritic cells) concomitantly added to ct (carboplatin/paclitaxel) - Arm A (A) vs DCVAC/LuCa + immune modulators (IFN-α and hydroxychloroquine) - Arm B (B)+ct vs ct - Arm C (C) in NSCLC patients (pts). Randomization 1:1:1; pts in A and B received up to 15 doses of DCVAC, ct was given 4-6 cycles in A and C. Stage IV NSCLC was confirmed histologically or cytologically, ECOG 0-1 pts were eligible. Stratification was done by histology subtype and smoking history. Primary efficacy analysis compared A vs C only as enrollment to B was closed early based on Sponsor’s assessment of further clinical development potential, there were no safety concerns or signals. Results: 112 pts at 12 sites were randomized (A/45 B/29 C/38). Patients characteristics were comparable across the study groups with the exception of gender (m/f, %: 65/35 (A) and 74/26 (C) and smoking history (75 % of smokers in A, 97 % in C). Median follow up time was 25.8 months, range 0.1-41.8. Median OS was 15.5 months in A compared to 11.8 months in C, hazard ratio (HR) 0.55, p-value 0.0232, 95% CI [0.33, 0,93], data maturity 77%. Median PFS was 6.74 in A and 5.63 months in C, HR 0.59, p-value 0.0415, 95% CI [0.36, 0.99], data maturity 86%. Overall response rate was 45% in A vs 34% in C. Most TEAEs were related to ct (anemia [35%-A, 32%-C], neutropenia [48% in A, 21%-C], thrombocytopenia [25% in A, 27% in C]). There were no grade ≥ 3 TEAEs solely related to DCVAC. Most common leukapheresis (lp)-related AE was vomiting in 2 pts out of 67 pts undergone lp. Conclusions: Addition of DCVAC-based immunotherapy to the standard of care chemotherapy significantly improved OS in stage IV NSCLC. Clinical trial information: NCT02470468.

A combination of vinorelbine and cisplatin is a standard treatment in non-small-cell lung cancer; oral vinorelbine is registered in 45 countries. Pemetrexed and cisplatin are recommended in front-line chemotherapy of non-squamous non-small-cell lung cancer (NS-NSCLC). The objective of this study was to conduct a cost minimization analysis from the perspective of the national health service (NHS) in each of 12 European countries, based on a randomized phase II study in NS-NSCLC (NAVoTRIAL01), with 100 oral vinorelbine plus cisplatin patients (arm A) and 51 pemetrexed plus cisplatin patients (arm B).Country-specific costs and DRG codes considered included those relating to anticancer drugs, administration settings (out-patient/in-patient/at home), serious adverse events (defined as involving hospitalization and considered due to anticancer drugs) and concomitant medications. Relevant costs were calculated based on country-specific reimbursement procedures and official tariffs.Cost and savings per patient.Using the NHS perspective, savings per patient treated with oral vinorelbine ranged from €1317 (Denmark) to €35,001 (Germany). Expressed as percentages, savings per patient treated with oral vinorelbine compared with pemetrexed ranged between 5% (France) and 83% (Czech Republic). Pooled average costs for each treatment arm across the 12 countries resulted in cost savings for payers of €12,871, favoring oral vinorelbine plus cisplatin.Given the reported efficacy with both regimens, this pan-European economic analysis provides compelling evidence supporting oral vinorelbine use over pemetrexed for the treatment of NS-NSCLC. Oral vinorelbine provides similar efficacy and an easily manageable safety profile at lower overall cost per patient treated, combined with an easier/more convenient mode of administration. Sensitivity analysis across varied scenarios demonstrated the robustness of the results. The principle weakness of our study was its reliance upon a single small scale study to provide efficacy data, since this is the only study conducted in this specific population of patients. Further large scale trials are needed to confirm these results.

Purpose Patients with extensive-stage disease small-cell lung cancer (SCLC) have poor survival outcomes despite first-line chemotherapy with etoposide and platinum. This randomized, double-blind phase III study evaluated the efficacy and safety of ipilimumab or placebo plus etoposide and platinum in patients with newly diagnosed extensive-stage disease SCLC. Patients and Methods Patients were randomly assigned at a ratio of one to one to receive chemotherapy with etoposide and platinum (cisplatin or carboplatin) plus ipilimumab 10 mg/kg or placebo every 3 weeks for a total of four doses each in a phased induction schedule (chemotherapy in cycles one to four; ipilimumab or placebo beginning in cycle three up to cycle six), followed by ipilimumab or placebo maintenance every 12 weeks. Primary end point was overall survival (OS) among patients receiving at least one dose of blinded study therapy. Results Of 1,132 patients randomly assigned, 954 received at least one dose of study therapy (chemotherapy plus ipilimumab, n = 478; chemotherapy plus placebo, n = 476). Median OS was 11.0 months for chemotherapy plus ipilimumab versus 10.9 months for chemotherapy plus placebo (hazard ratio, 0.94; 95% CI, 0.81 to 1.09; P = .3775). Median progression-free survival was 4.6 months for chemotherapy plus ipilimumab versus 4.4 months for chemotherapy plus placebo (hazard ratio, 0.85; 95% CI, 0.75 to 0.97). Rates and severity of treatment-related adverse events were similar between arms, except for diarrhea, rash, and colitis, which were more frequent with chemotherapy plus ipilimumab. Rate of treatment-related discontinuation was higher with chemotherapy plus ipilimumab (18% v 2% with chemotherapy plus placebo). Five treatment-related deaths occurred with chemotherapy plus ipilimumab and two with chemotherapy plus placebo. Conclusion Addition of ipilimumab to chemotherapy did not prolong OS versus chemotherapy alone in patients with newly diagnosed extensive-stage disease SCLC. No new or unexpected adverse events were observed with chemotherapy plus ipilimumab. Several ongoing studies are evaluating ipilimumab in combination with programmed death-1 inhibitors in SCLC.