TPS3165 Background: CEACAM5 is a cell surface glycoprotein that is overexpressed in various carcinomas, notably in gastric cancer (GC), non-small cell lung cancer (NSCLC), pancreatic adenocarcinoma (PDAC), and colorectal cancer (CRC), but shows limited expression on healthy adult cells. Precemtabart tocentecan is an investigational anti-CEACAM5 ADC (drug-to-antibody ratio: 8) that utilizes a unique linker–payload combination to selectively deliver the topoisomerase 1 inhibitor, exatecan, to CEACAM5 overexpressing tumor cells. Preliminary clinical data from the dose-escalation part of the first-in-human study of precemtabart tocentecan in patients with metastatic CRC (PROCEADE CRC-01) demonstrated a manageable and predictable safety profile and promising preliminary efficacy in 40 heavily pretreated patients. The PROCEADE PanTumor study is a Phase 1b/2, multicenter, open-label study that aims to investigate the clinical activity of precemtabart tocentecan, either as monotherapy or in combination with other anticancer agents, in patients with advanced GC, advanced NSCLC and advanced PDAC. Methods: The study was designed as a matrix study with a master protocol (applicable to all substudies) and three substudy protocols (GC; NSCLC; PDAC). Based on the master protocol, patients aged ≥18 years, with an Eastern Cooperative Oncology Group performance status ≤1, adequate baseline hematological, renal, and hepatic function, ≥1 lesion that is measurable using RECIST v1.1, who have received ≥1 prior line of treatment are eligible. Patients must have an archival formalin-fixed paraffin-embedded tumor tissue or a fresh biopsy. In the respective substudies, patients with advanced or metastatic, HER2-negative GC or gastroesophageal junction adenocarcinoma; patients with advanced (Stage III; ineligible for resection/curative radiation) or metastatic NSCLC; or patients with advanced or metastatic PDAC will be included. Patient selection will be based on CEACAM5 expression level (both high and low in GC, only high in NSCLC and PDAC [CEACAM5 high : ≥50% tumor cells with immunohistochemistry [IHC] ≥2+ staining; CEACAM5 low : <50% tumor cells with IHC ≥2+ staining]), and in patients with NSCLC, EGFR mutation status ( EGFR -wt and EGFR mut+). The primary endpoint is objective response (proportion of patients with confirmed complete/partial response [CR/PR] per RECIST v1.1, assessed by investigator). Secondary endpoints include adverse events, duration of response (RECIST v1.1), disease control (CR, PR, stable disease, or non-CR/non-progressive disease [PD] at Week 12), time to response, progression-free survival, and pharmacokinetic assessments. The study is planned to be initiated at multiple sites globally, with an estimated enrollment of 250 patients. Copyright © 2025 AACR. Originally presented at AACR 2025. Reprinted with permission. Clinical trial information: NCT06710132 .

3038 Background: CEACAM5 is overexpressed in ~90% of CRCs, with limited expression on healthy cells. Precemtabart tocentecan (M9140), the first anti-CEACAM5 ADC with an exatecan payload (topoisomerase 1 inhibitor), showed a predictable, manageable safety profile and promising early clinical activity in the dose escalation of the Phase 1 PROCEADE-CRC-01 study (NCT05464030) in heavily pretreated patients with mCRC. Methods: This global Phase 1 study in 3L adult patients with locally advanced/mCRC (ECOG PS ≤1; previous irinotecan therapy) evaluates clinical activity, safety, and tolerability of precemtabart tocentecan. Here, we report on dose optimization of precemtabart tocentecan tested at 2.8 mg/kg Q3W (Arm A1) or 2.4 mg/kg Q3W (A2; 1:1 randomization) to select the recommended phase 2 dose (RP2D). Results: As of Jan 2025, 60 patients (recruited Apr–Oct 2024) had been treated (A1, n = 29; A2, n = 31). Median age was 60.0 years, and 51.7% were male. In A1, 18 (62.1%) patients remained on treatment and 16 (51.6%) in A2. Treatment-emergent AEs (TEAEs) were reported in all patients; grade ≥3 in 38 (63.3%) patients (A1: n = 19 [65.5%]; A2: n = 19 [61.3%]); anemia and neutropenia (any grade; grade ≥3) were most common. Serious TEAEs were reported in 18 (30.0%) patients (A1: n = 8 [27.6%]; A2: n = 10 [32.3%]). Grade ≥3 hematologic AEs were reported in 32 (53.3%) patients: anemia (A1, n = 9; A2, n = 10), neutropenia (A1, n = 14; A2, n = 12), thrombocytopenia (n = 6 both), leukopenia (A1, n = 7; A2, n = 6), lymphopenia (A1, n = 1; A2, n = 2), febrile neutropenia (n = 3 both), and pancytopenia (A1, n = 0; A2, n = 1). Treatment was discontinued in 26 (43.3%) patients (A1: progressive disease (PD), n = 9, patient withdrawal, n = 1, other, n = 1; A2: PD, n = 14, death, n = 1). No treatment-related deaths were reported. Overall, PK profiles were consistent with previous data, with overlap attributed to high between-subject variability. Partial responses were reported in 7 (24.1%; n = 4 [13.8%] confirmed) patients in A1 and 3 (9.7%; n = 1 [3.2%] confirmed) in A2 (all responders remain on treatment), stable disease in 15 (51.7%) and 21 (67.7%), and PD in 5 (17.2%) and 6 (19.4%) patients, respectively. DCR at 12 weeks was 72.4% in A1 and 67.7% in A2. Conclusions: These preliminary results corroborate the encouraging efficacy and safety data from the dose escalation part of the PROCEADE CRC-01 study, with no new relevant safety findings. ORR was higher at 2.8 mg/kg, with similar tolerability at both doses. The ORR of 24.1% (13.8% confirmed) at 2.8 mg/kg compares favorably with current monotherapy SoCs (ORRs 1-2%) and recent phase 3 data with trifluridine–tipiracil + bevacizumab (ORR 6.1%) in 3L+ mCRC. These results suggest 2.8 mg/kg as the RP2D for further development in CRC, and other solid tumors (NCT06710132). More mature data, including PFS, will be presented at the congress. Clinical trial information: NCT05464030 .

3000 Background: CEACAM5 is a cell surface protein with limited expression in adult healthy tissues, but high expression in various adenocarcinomas, particularly in CRC (>90% of pts). M9140 is the first anti-CEACAM5 ADC with a topoisomerase 1 inhibitor (Top1i) payload (exatecan). The ß-glucuronide linker connecting the M9140 antibody backbone to the payload is highly stable in circulation (drug-to-antibody ratio=8). In preclinical models, M9140 has demonstrated strong potency, antitumor activity, and a bystander effect. Methods: This Phase 1 trial (NCT05464030) investigated the safety, tolerability, pharmacokinetics (PK), and preliminary clinical activity of M9140 as monotherapy (Q3W [Day 1 of 21-day cycles]; IV) in adults with CRC (ECOG PS ≤1) who had received ≥2 prior lines of treatment. The primary objectives of Part 1A were to determine the maximum tolerated dose (MTD) and/or recommended dose(s) for expansion (RDE). Results: At data cutoff (19 Jan 2024), 40 pts from the US, EU, and Japan were treated across 7 dose levels (DLs): 0.6 mg/kg, 1.2 mg/kg (n=3, each), 2.4 mg/kg (n=7), 2.6 mg/kg (n=4), 2.8 mg/kg (n=12), 3.0 mg/kg (n=4), and 3.2 mg/kg (n=7, including 3 pts with primary G-CSF prophylaxis). Most pts were heavily pretreated (80% had ≥3 lines of prior treatment; 100% received irinotecan). Overall, 6 pts experienced dose-limiting toxicities (DLTs); the majority were hematological adverse events at DLs 3.0 and 3.2 mg/kg; 1 patient (at 2.8 mg/kg) experienced a Grade 5 sepsis. The most frequently reported Grade ≥3 treatment-emergent adverse events (TEAEs) were neutropenia in 16 (40.0%) pts, thrombocytopenia and anemia in 11 (27.5%) pts each, and WBC decreased in 10 (25.0%) pts. No events of ocular toxicity/interstitial lung disease (ILD) were reported. The best objective response per RECIST v1.1 was partial response (PR) in 4 (10.0%) pts (3 confirmed) (all at DLs ≥2.4 mg/kg); stable disease (SD) in 17 (42.5%), including 6 (15.0%) lasting for ≥100 days and progressive disease (PD) in 6 (15.0%) pts. For a total of 13 (32.5%) pts, the best overall response was not evaluable, including 6 (15.0%) who had no on-treatment tumor assessment yet. The preliminary median progression-free survival (PFS) was 6.7 months (95% CI: 4.6, 8.4). As of data cutoff, 15 (37.5%) pts are continuing treatment. Based on the safety, tolerability, preliminary clinical activity, PK, and PK/pharmacodynamics modeling data, 2.8 mg/kg was declared as the MTD, and 2.4 mg/kg and 2.8 mg/kg were chosen as the RDEs and have been taken forward into a randomized expansion study. Conclusions: M9140 demonstrated encouraging activity in heavily pretreated pts with advanced CRC, with a manageable and predictable safety profile. Contrary to approved ADCs with Top1i payloads, no ILD or ocular toxicities were observed. Evaluation of M9140 in mCRC continues in the dose expansion part of this study. Clinical trial information: NCT05464030 .

The primary objective of this multicentric dose allocation and dose expansion study was to determine the MTD and the DLTs of the lucitanib (a tyrosine kinase inhibitor of the FGFR/VEGFR/PDFGR pathways)/fulvestrant combination. Postmenopausal women with ER+/HER2− mBC, who have relapsed during or after treatment with fulvestrant, were eligible. The study had a dose allocation part to assess the tolerability of the combination followed by a dose expansion part. Eighteen patients with ER+, mBC were enrolled; median age was 66 years, 50% had a PS: 0 and all had received previous endocrine treatment. The study was prematurely terminated after 18 patients (15 in part 1 and 3 in part 2) based on preclinical experiments that failed to confirm the hypothesis that addition of lucitanib would reverse sensitivity to endocrine treatments. Based on data of global lucitanib development, it was decided to stop the dose allocation at 12.5 mg and to start the dose expansion part at 10 mg/day. The most common grade ≥ 3 toxicities (> 10% of patients) were hypertension (78%) and asthenia (22%). All patients required at ≥ 1 interruption, 13 patients (72%) required ≥ 1 dose reduction. Three patients (72%) withdrew from the study for AEs (at 10 mg). Three patients achieved a confirmed PR (10 mg n = 1; 12.5 mg n = 2). Although the combination is feasible it requires close monitoring of the patients for the management of adverse events. Further investigation is required to better understand the potential role of FGFR inhibition in reversing resistance to endocrine treatment.

Abstract FGFR1 amplification could mediate resistance to endocrine therapy and FGFR1 inhibition reverses this resistance. This phase Ib seeks to evaluate whether the combination of lucitanib, a potent FGFR/VEGFR/PDFGR inhibitor, in combination with fulvestrant, an endocrine agent, reverses resistance to fulvestrant. Eligible patients for this study were postmenopausal with ER+/HER2- mBC and have relapsed during or after treatment with fulvestrant. There were 2 parts in the study: a dose allocation to assess the tolerability of the combination in terms of DLTs and MTD using a modified Continual Reassessment Method (mCRM) [part I] and a dose expansion, with patients assigned to 2 different cohorts based on FGFR amplification, to further evaluate the tolerability of the combination and to identify the recommended phase II dose (RP2D) [part II]. Surrogate target hitting biomarkers were also dosed at baseline and on-treatment. The sponsor decided to halt the clinical development in mBC indication and the study was prematurely terminated after 18 patients (15 in part I and 3 in part II). The presentation will focus on these 18 patients. Patients had ECOG PS 0 or 1 and median number of previous treatments in metastatic setting was 3. Two doses of lucitanib (10mg daily n=9 and 12.5mg daily n=6) in combination with 500 mg/month of fulvestrant were tested in part I. At the 10mg dose level, one patient experienced a DLT (grade 3 hypertension). Based on global lucitanib development program data, it was decided to start Part II with lucitanib 10mg daily. The most common related grade ≥3 toxicities occurring in more than 10% of patients were hypertension (78%) and asthenia (22%). All patients required at least one dose interruption mainly for toxicities, while 13 patients (72%) required at least a dose reduction for toxicities. Thirteen patients (72%) withdrew from the study for disease progression, 3 (17%) for adverse events (at 10mg) and 2 (11%) for non-medical reasons. Three patients achieved a confirmed partial response (as per RECIST v1.1), one at 10mg and two at 12.5mg. About 55% of the patients experienced clinical benefit with a median duration of the benefit of 39.6 weeks and a maximun duration of the benefit of 79.1 weeks for 1 patient (PR at Cycle 4). Biomarker modulations were consistent with lucitanib mode of action; targeting VEGFRs (significant increase of VEGFA, IL8, PlGF) and FGFR1 (significant increase of FGF23). The combination is feasible but requires close patient monitoring and intensive management of adverse events. Those are in line with the anti-angiogenic activity of lucitanib. 10mg (N=12)12.5mg (N=6)All (N=18)Objective Response Rate (ORR)n(%) 11 (8.3)2 (33.3)3 (16.7) 95% CI 3[1.5;35.4][9.7;70.0][5.8;39.2]Clinical Benefit Rate (CBR)n(%) 24 (33.3)6 (100.0)10 (55.6) 95% CI 3[13.8;61.0][61.0;100.0][33.7;75.4]Duration of Clinical Benefitmedian (weeks)28.171.339.6 95% CI 3[27.9; 32.7][29.1; 79.1][27.9; 79.1]1: CR or PR 2: CR or PR or stabilization (SD or NonCR/NonPD) >24 weeks or at end of cycle 6 3: 95% Wilson method of Confidence interval of the estimate Citation Format: Campone M, Bachelot T, Penault-Llorca F, Pallis A, Agrapart V, Pierrat M-J, Poirot C, Paux G, Dubois F, Xuereb L, Robert R, Andre F. A phase Ib study of oral administration of lucitanib in combination with fulvestrant in patients with HR+ metastatic breast cancer (mBC) [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-09-11.

Erlotinib has been approved for the management of NSCLC patients after failure of the first or subsequent line of chemotherapy. Although the efficacy of erlotinib is clearly associated with the presence of EGFR mutations, there is a subset of patients with EGFR wild-type (EGFRwt) tumors who impressively respond.

Background: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors α/β (PDGFRα/β). FGF aberrancy, as defined by amplification of either FGFR1, or 11q (containing FGF ligands 3, 4, CCND1, and 19), or both, is a hallmark genomic alteration that can be observed in up to 25% of patients with breast cancer. In a phase I clinical trial of lucitanib at daily doses of 5 to 20 mg, heavily pretreated patients with advanced breast cancer patients and FGF aberrancy experienced an objective response rate (ORR) of 50% and a median progression-free survival (PFS) over 9 months (Soria et al, 2014). This compelling clinical activity has led to the initiation of a global clinical development program for lucitanib in breast cancer. Trial design: this is a phase II trial testing the efficacy of lucitanib at the dose of 15 mg daily in patients with ER+/HER2- metastatic breast cancer who have received at least one first-line systemic anticancer therapy in the metastatic setting. After informed consent, metastatic tissue (fresh biopsy or archival) is centrally evaluated by FISH for FGFR1- and/or 11q- amplification. Based on FISH results, patients are allocated to cohort 1 (FGFR1-amp), cohort 2 (11q-amp) or cohort 3 (neither). Patients with dual amplification are allocated to cohort 1. The primary objective is to evaluate the ORR of single agent lucitanib in the three cohorts. Secondary objectives include clinical benefit rate, PFS, safety and pharmacokinetics in addition to exploratory biomarker analyses. A Simon two-stage design will be used for each of the cohorts to test the null hypothesis that the ORR is 5% or less versus 20% using a one-sided test with 5% level of significance and 90% power. In each cohort separately, an initial 21 patients with measurable disease at baseline will be assessed at the end of stage 1. If at least 2 patients respond per the pre-specified criteria, this cohort will accrue additional 20 patients. The null hypothesis will be rejected if there are at least 5 responders among all 41 patients. Eligibility Criteria: ER+/HER2- metastatic breast cancer who have received at least a first line of systemic anticancer therapy and no more than 2 line of chemotherapy with or without targeted therapy in the metastatic setting and have ECOG performance status ≤ 2. Patients with uncontrolled hypertension and at risk of developing hypertension related complications are not eligible. Conclusion: FINESSE is a phase II trial testing lucitanib, a multikinase inhibitor, in three selected populations in order to investigate the ORR in FGFR1 or 11q amplified or non-amplified populations and to explore the role of FGFR1 or 11q amplifications through correlative translational analyses. As of May 21st 2015, 40 patients have been enrolled, 19 of them in the FGFR1-amplified arm. Citation Format: Andre F, Daly F, Azim Jr HA, Agrapart V, Fumagalli D, Gingras I, Guitart M, Lange A, Turner NC, Pierrat M-J, Loibl S, Poirot C, Curigliano G, Loi S, Pallis A, Piccart M, Cortes J. FINESSE - An open, 3-cohort, phase II trial testing oral administration of lucitanib in patients with FGFR1-amplified or non-amplIfied oestrogeN rEceptor poSitive metaStatic breast cancEr. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-03.

Abstract Background: Lucitanib is a potent, oral inhibitor of the tyrosine kinase activity of Fibroblast Growth Factor Receptors 1-3 (FGFR1-3), Vascular Endothelial Growth Factor Receptors 1-3 (VEGFR1-3) and Platelet-Derived Growth Factor Receptors α/β (PDGFRα/β). FGF aberrancy, as defined by amplification of either FGFR1, or 11q (containing FGF ligands 3, 4, CCND1, and 19), or both, is a hallmark genomic alteration that can be observed in up to 25% of patients with breast cancer. In a phase I clinical trial of lucitanib at daily doses of 5 to 20 mg, heavily pretreated patients with advanced breast cancer patients and FGF aberrancy experienced an objective response rate (ORR) of 50% and a median progression-free survival (PFS) over 9 months (Soria et al, 2014). This compelling clinical activity has led to the initiation of a global clinical development program for lucitanib in breast cancer. Trial design: this is a phase II trial testing the efficacy of lucitanib at the dose of 15 mg daily in patients with ER+/HER2- metastatic breast cancer who have received at least one first-line systemic anticancer therapy in the metastatic setting. After informed consent, metastatic tissue (fresh biopsy or archival) is centrally evaluated by FISH for FGFR1- and/or 11q- amplification. Based on FISH results, patients are allocated to cohort 1 (FGFR1-amp), cohort 2 (11q-amp) or cohort 3 (neither). Patients with dual amplification are allocated to cohort 1. The primary objective is to evaluate the ORR of single agent lucitanib in the three cohorts. Secondary objectives include clinical benefit rate, PFS, safety and pharmacokinetics in addition to exploratory biomarker analyses. A Simon two-stage design will be used for each of the cohorts to test the null hypothesis that the ORR is 5% or less versus 20% using a one-sided test with 5% level of significance and 90% power. In each cohort separately, an initial 21 patients with measurable disease at baseline will be assessed at the end of stage 1. If at least 2 patients respond per the pre-specified criteria, this cohort will accrue additional 20 patients. The null hypothesis will be rejected if there are at least 5 responders among all 41 patients. Eligibility Criteria: ER+/HER2- metastatic breast cancer who have received at least a first line of systemic anticancer therapy and no more than 2 line of chemotherapy with or without targeted therapy in the metastatic setting and have ECOG performance status ≤ 2. Patients with uncontrolled hypertension and at risk of developing hypertension related complications are not eligible. Conclusion: FINESSE is a phase II trial testing lucitanib, a multikinase inhibitor, in three selected populations in order to investigate the ORR in FGFR1 or 11q amplified or non-amplified populations and to explore the role of FGFR1 or 11q amplifications through correlative translational analyses. As of May 21st 2015, 40 patients have been enrolled, 19 of them in the FGFR1-amplified arm. Citation Format: Andre F, Daly F, Azim Jr HA, Agrapart V, Fumagalli D, Gingras I, Guitart M, Lange A, Turner NC, Pierrat M-J, Loibl S, Poirot C, Curigliano G, Loi S, Pallis A, Piccart M, Cortes J. FINESSE - An open, 3-cohort, phase II trial testing oral administration of lucitanib in patients with FGFR1-amplified or non-amplIfied oestrogeN rEceptor poSitive metaStatic breast cancEr. [abstract]. In: Proceedings of the Thirty-Eighth Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2015 Dec 8-12; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2016;76(4 Suppl):Abstract nr OT1-03-03.

Surgery remains the only curative treatment modality for patients with stage I–IIIA non-small cell lung cancer (NSCLC). However, even after complete resection, the risk of recurrence is substantial, and 5-year overall survival (OS) is approximately 70% for patients with stage IB disease, 40–50% for stage II and less than 30% for stage IIIA patients. Efforts to improve the survival of patients with operable NSCLC have examined the addition of chemotherapy (CMT) and/or radiotherapy (RT) in the post-operative setting.

In the present phase I/II study, the biweekly carboplatin (area under the curve, 2.5) plus gemcitabine (1100 mg/m(2)) combination in patients aged >= 70 years with advanced and metastatic squamous non-small-cell lung cancer achieved an overall response rate of 35.8%, a median progression-free survival of 6.7 months, and a median overall survival of 13.3 months, with favorable toxicity.Background: The present study was a phase I/II study to determine the maximum tolerated doses (MTDs) and dose-limiting toxicities of the biweekly carboplatin/gemcitabine combination and evaluate its safety and efficacy in patients aged >= 70 years with advanced squamous non-small-cell lung cancer (NSCLC). Patients and Methods: Patients aged >= 70 years with advanced or metastatic squamous NSCLC received escalated doses of carboplatin (area under the curve [AUC] 2-2.5 intravenously) and gemcitabine (800-1100 mg/m(2) intravenously) every 2 weeks (phase I). In the phase II, the drugs were administered at their previously defined MTDs (carboplatin, AUC 2.5; gemcitabine, 1100 mg/m(2)). The primary endpoint was the overall response rate. Results: A total of 69 patients were enrolled (phase I, n - 15). The median age was 76 years (range, 70-84 years); 52 patients had stage IV disease, and 61 and 8 patients had Eastern Cooperative Oncology Group performance status of 0 to 1 and 2, respectively. The MTDs could not be reached at the predefined last dose levels. The dose-limiting toxicities were grade 5 renal toxicity and grade 3 thrombocytopenia. In the phase II study, the overall response rate was 35.8% (95% confidence interval [CI], 23.0%-48.8%). In the intention-to-treat analysis, the median progression-free survival was 6.7 months (95% CI, 4.2-8.8 months), and the median overall survival was 13.3 months (95% CI, 7.1-19.6 months). Grade 3 or 4 neutropenia was observed in 7 patients (12.3%), grade 3 or 4 thrombocytopenia in 4 patients (7.1%), and grade 2 or 3 fatigue in 10 patients (17.5%). One toxic death occurred in the phase I of the study. Conclusion: The biweekly regimen of gemcitabine and carboplatin showed satisfactory efficacy and a favorable toxicity profile in elderly patients with advanced or metastatic squamous cell NSCLC. (C) 2016 Elsevier Inc. All rights reserved.

Aim/Background: AL3810 (lucitanib) is a potent, oral tyrosine kinase inhibitor of FGFR1-3, VEGFR1-3 and PDGFR&agr;/&bgr;. These well-described signaling pathways are essential for tumor growth, survival, migration, and angiogenesis. This study aims to evaluate the safety of AL3810 in Chinese patients with advanced solid tumors. Methods: This phase I, single-center study evaluated the tolerability of oral AL3810 in terms of Maximum Tolerated Dose (MTD), Dose-Limiting Toxicities (DLTs), and aimed to identify the Recommended Dose (RD). A 3 + 3 dose escalating design was used. Initial dose levels to be tested were 10mg, 15mg and 20mg daily on a continuous basis. Moreover, up to 12 patients were to be included at the RD level to confirm the RD based on safety and efficacy evaluation. PK analysis using a non-compartmental PK population modeling approach will be performed. Results: As of August 2015, 16 patients (pts) were treated with AL3810, 14 were female, median age was 56 yrs (range 28-64) with ECOG 0/1 in 1/15 pts. During the escalation part, 10mg and 15mg dose levels were explored. Two DLTs occurred at 15mg daily dose out of 5 patients (fatigue Gr 3 and direct bilirubin increase Gr 3,). Therefore 15mg dose level was defined as the MTD and 10mg as the RD. Currently, 8 additional pts are enrolled at this dose level to confirm the RD. Common Gr 2-3 adverse events occurring in ≥ 3pts were hypertension (10 pts), hypothyroidism (9 pts), proteinuria (6 pts), fatigue (3 pts), decreased appetite (3 pts), and white blood cell count decreased (3 pts). Two pts with metastatic breast cancer, treated at 10mg daily, had a confirmed Partial Response according to RECIST. Disease stabilization of 4 months was observed in pt with ovarian cancer treated at 10 mg. Conclusions: This phase I trial, testing for first time AL3810 in Chinese patients, identified 15mg daily as the MTD and 10mg as the RD for future studies. Expansion cohorts are planned in different indications. Clinical trial identification: CL1-8088-005 Disclosure: L. Jiang, X. Ma, J. Pang: employee of HaiHe pharmaceutical. A. Kanehisa, F. Legrand, A. Pallis, G. Paux, R. Robert: employee at Institut de Recherches Internationales Servier (IRIS). X. Chen, P. Letecheur, L. Qiang: employee at ICTR China. J. Ding: employee of SIMM. All other authors have declared no conflicts of interest.

Non-small-cell lung cancer (NSCLC) is a very common disease in the elderly population and its incidence in this particular population is expected to increase further, because of the ageing of the Western population. Despite this, limited data are available for the treatment of these patients and, therefore, the development of evidence-based treatment recommendations is challenging. In 2010, European Organization for Research and Treatment of Cancer (EORTC) took an initiative in collaboration with International Society of Geriatric Oncology (SIOG) and created an experts panel that provided an experts' opinion consensus paper for the management of elderly NSCLC patients. Since this publication, important new data are available and EORTC and SIOG recommended to update the 2010 recommendations. Besides recommendations for surgery, adjuvant chemotherapy and radiotherapy, treatment of locally advanced and metastatic disease, recommendations were expanded, to include data on patient preferences and geriatric assessment.

PURPOSE:To examine availability of Palliative Care (PC) services and referral patterns of European Lung cancer specialists to PC.METHODS:All members of the EORTC Lung Cancer Group (LCG) were asked via email to participate in an on-line survey.RESULTS:50 out of 170 (29.4%) replied: 24 medical oncologists, 14 radiation/clinical oncologists, 11 pulmonologists and 1 thoracic surgeon. All but two of respondents (96%) had access to at least one component of PC services. In terms of referral of patients to PC almost 75% of respondents would refer most of their patients when there were no treatment options or at the end of life, while only 22% would refer patients at earlier stages of disease. Barriers for referral to PC were negative attitudes of patients to PC (26%), lack of availability of PC services (20%), lack of expertise of PC physicians(18%), the belief that referral to PC signifies abandoning patients (8%), and that PC specialists discourage active oncological therapy (8%). Whilst most of the respondents expressed positive attitudes, 12-22% had overtly negative attitudes towards PC. Seventy-eight (78%) of respondents expressed an interest to participate in a trial of early PC (EPC).CONCLUSION:Despite good availability of SPC services at institutions of members of the EORTC LCG, and most respondents expressing positive attitudes towards PC, their practice involved referral of patients to PC late in the disease trajectory, hence Lung Cancer specialists in Europe have not adopted the practice of EPC concurrent with active oncological care.

Response criteria have always been difficult to apply to malignant pleural mesothelioma (MPM), due to its unique pattern of growth. We developed some models to show that progression free survival rate (PFSR) could be a better predictor of overall survival (OS) than the response rate (RR) in MPM patients. The results were validated independently in the European Organisation for Research and Treatment of Cancer (EORTC) 08052, a phase II study in MPM.Individual patient data from 10 EORTC-Lung Cancer Group (LCG) studies of first-line chemotherapy in MPM were pooled. Response to therapy was assessed according to World Health Organisation (WHO) criteria in all except the two most recent trials, which used Response Evaluation Criteria in Solid Tumours (RECIST). Landmark analyses (LA) at 9 weeks and 18 weeks after registration/randomisation were performed to assess the association between PFSR and OS. Independent validation of the results was conducted in EORTC 08052 study (82 patients) employing the same LA.All 10 studies (N=523 patients) were included in the LA of PFSR at 9 and 18 weeks (PFSR-9 and PFSR-18). PFSR-9 and PFSR-18 were confirmed as predictors of OS, with hazard ratio (HR) of 0.37 (95% confidence interval (CI), 0.30-0.47) and 0.50 (0.38-0.65) and C-index of 0.62 and 0.58, respectively. In the validation study, 28.4% achieved CR/PR and 77.8% had disease control (CR/PR/SD) as their best overall response. PFSR-9 and PFSR-18 weeks were both strongly correlated with OS (HR of 0.35 [80% CI, 0.25-0.49] and 0.46 (0.32-0.67) and C-index of 0.66 and 0.60, respectively).PFSR-18 was strongly correlated and discriminated patients with better OS from the poorer prognosis patients. An earlier end-point, PFSR-9 was also strongly correlated to OS with better discriminating capacity. The results were independently validated.

Small-cell lung cancer represents about 15% of all lung cancers; increasingly, randomised controlled trials of this disease measure the health-related quality of life of patients. In this Systematic Review we assess the adequacy of reporting of health-related quality-of-life methods in randomised controlled trials of small-cell lung cancer, and the potential effect of this reporting on clinical decision making. Although overall reporting of health-related quality of life was acceptable, improvements are needed to optimise the use of health-related quality of life in randomised controlled trials.

Objectives: Vulnerability assessment of geriatric patients with cancer may contribute to improved anti-cancer treatment with maximal results and minimal side effects. The aim of the present study was to evaluate whether the Vulnerable Elders Survey-13 (VES-13) score is associated with completion of radiotherapy among elderly patients with cancer.Materials and Methods: This was a prospective observational study that included patients greater than age 75 with histologically confirmed cancer disease, referred to the Department of Radiation Oncology to receive radical or palliative radiotherapy, from 2010 to 2012. VES-13 forms were filled in before the initiation of radiotherapy and scores were assigned according to a standardized scoring procedure.Results: Of a total of 230 participants (median age 78.5 years), 41 (17.8%) did not complete radiotherapy. These patients had higher VES-13 scores (median with interquartile range: 5 [2-8.5]) compared to those who completed the treatment (3 [1-7]; P = 0.008). A VES-13 score > 3 was associated with 2.14 times higher probability of not completing radiotherapy, whereas in patients with scores > 7 this probability was 3.34 times higher. The association between higher VES-13 scores and non-completion of radiotherapy was independent of other factors, such as age, sex, comorbidities, type of radiotherapy, and presence of side effects.Conclusion: Patients with higher VES-13 scores had increased probability of not completing radiotherapy in our study, and this effect was independent of other factors that might affect radiotherapy completion. (C) 2013 Elsevier Ltd. All rights reserved.

Older people represent the majority of cancer patients but their specific needs are often ignored in the development of health-related quality of life (HRQOL) instruments. The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-ELD15 was developed to supplement the EORTC’s core questionnaire, the QLQ-C30, for measuring HRQOL in patients aged >70 years in oncology studies. Patients (n=518) from 10 countries completed the QLQ-C30, QLQ-ELD15 and a debriefing interview. Eighty two clinically stable patients repeated the questionnaires 1 week later (test–retest analysis) and 107 others, with an expected change in clinical status, repeated the questionnaires 3 months later (response to change analysis, RCA). Information from the debriefing interview, factor analysis and item response theory analysis resulted in the removal of one item (QLQ-ELD15→QLQ-ELD14) and revision of the proposed scale structure to five scales (mobility, worries about others, future worries, maintaining purpose and illness burden) and two single items (joint stiffness and family support). Convergent validity was good. In known-group comparisons, the QLQ-ELD14 differentiated between patients with different disease stage, treatment intention, number of comorbidities, performance status and geriatric screening scores. Test–retest and RCA analyses were equivocal. The QLQ-ELD14 is a validated HRQOL questionnaire for cancer patients aged ⩾70 years. Changes in elderly patients’ self-reported HRQOL may be related to both cancer evolution and non-clinical events.

It is estimated that approximately 25% of all lung cancer cases are observed in never-smokers and its incidence is expected to increase due to smoking prevention programs. Risk factors for the development of lung cancer described include second-hand smoking, radon exposure, occupational exposure to carcinogens and to cooking oil fumes and indoor coal burning. Other factors reported are infections (HPV and Mycobacterium tuberculosis), hormonal and diatery factors and diabetes mellitus. Having an affected relative also increases the risk for lung cancer while recent studies have identified several single nucleotide polymorphisms associated with increased risk for lung cancer development in never smokers. Distinct clinical, pathology and molecular characteristics are observed in lung cancer in never smokers; more frequently is observed in females and adenocarcinoma is the predominant histology while it has a different pattern of molecular alterations. The purpose of this review is to summarize our current knowledge of this disease.