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9561 Background: Medical treatment of lung cancer has irreversibly changed since the development of immune checkpoint inhibitors (ICI). However, immune biomarkers of efficacy are still lacking. Preliminary data in leukemia and pancreatic cancer showed that soluble immune checkpoints are associated with a reduced overall survival (OS). This led us to explore the prognostic and predictive value of soluble immune checkpoints in non-small cell lung cancer (NSCLC) patients treated with chemotherapy or ICI. Methods: We analyzed 90 advanced NSCLC patients. The pilot cohort (Rennes University Hospital, France), included 48 patients treated with platinum doublets (n = 33) or ICI (n = 15) (LOC/11-16 protocol). The confirmation cohort (Paoli-Calmettes Institute) included 42 patients treated with ICI (nivolumab or pembrolizumab) in a longitudinal prospective setting (Immunosup trial, NCT03595813). In both cohorts, enzyme-linked immunosorbent assays (ELISA) were performed in baseline plasma samples for soluble forms of PD-1, PD-L1, global BTN3, BTLA, BTN3-A1 and BTN2A1. Soluble ICI levels were linked to clinical data using Kaplan-Meier, log-rank and Cox proportional-hazards models. Cut-points were determined using maxstat package for survival, R software R 3.6.2. Results: Five soluble immune checkpoints correlated and clustered together in unsupervised analysis (PD-1, PD-L1, global BTN3, BTLA, BTN3-A1), but were not associated with ICI efficacy. In patients treated with ICI, in the pilot and confirmation cohort, a high baseline plasmatic concentration of soluble BTN2A1 was significantly associated with an improved OS (confirmation cohort with a BTN2A1 cut-point of 3.55 ng/ml: HR = 0.30, 95%CI = 0.12-0.74, p = 0.0057, median OS in BTN2A1low = 7.6 months and median OS in BTN2A1hi = 19.5 months). On the contrary, in patients treated with chemotherapy, soluble BTN2A1 concentration was not associated with overall survival. Conclusions: In advanced NSCLC patients, a high baseline plasmatic concentration of soluble BTN2A1 was correlated with improved outcomes for ICI, but not for chemotherapy, suggesting that baseline soluble BTN2A1 level is a potential predictive biomarker of ICI efficacy. Additional studies are ongoing to confirm this finding.

Purpose Surgical resection plus adjuvant platinum-based chemotherapy is considered standard care for stage II to III non–small-cell lung cancer (NSCLC), but its efficacy is limited, and it involves toxic risks, justifying patient-tailored treatment. Excision repair cross-complementation group 1 (ERCC1) was shown to predict cisplatin-based chemotherapy response; EGFR mutations were predictive of epidermal growth factor receptor inhibition response. Patients and Methods This prospective randomized phase II trial enrolled 150 patients with completely resected non–squamous cell stage II or IIIA (non-N2) tumors. Patients in the control arm (n = 74) were treated with four standard-dose courses of cisplatin plus pemetrexed (CP). In the customized treatment arm (n = 76), patients with activated EGFR mutations received erlotinib 150 mg for 1 year; ERCC1-negative patients received four CP courses, whereas ERCC1-positive patients underwent follow-up. The trial sought to demonstrate the feasibility of customized adjuvant chemotherapy based on timely biomarker analysis within a 2-month postsurgery delay. Secondary objectives were tolerability, compliance with adjuvant therapy, and biomarker distribution. Results In arm A, all patients received CP; in arm B, seven received erlotinib, 53 were administered CP, and 16 underwent follow-up. Median erlotinib exposure was 344 days. Of the 127 patients allocated to CP, 82% received four cycles with good tolerability. The overall success rate of the trial (ie, percentage of patients with complete biomarker status able to start adjuvant treatment within 2 months of surgery) was 80%. Conclusion The primary end point of the trial was met, demonstrating the feasibility of a national biology-driven trial in the adjuvant NSCLC setting. Nevertheless, the phase III part was canceled because of the unreliability of the ERCC1 immunohistochemical readouts.

e15690 Background: NeuroEndocrine Tumors (NETs) remain a poorly known entity, especially in older patients. The therapeutic management is multidisciplinary combining surgery, interventional radiology, chemotherapy, cancer supportive care and also geriatrics oncology. The aim of this study performed by the OncoGeriatry Coordination Unit (UCOG) of Brittany, in collaboration with the National Reference Network for the management of NET (RENATEN), was to analyze the current management of NETs in older patients (more than 75 years old) and to develop recommandations to optimize the management of elderly patients with NENs. RENATEN’s guidelines mean systematic discussion of the cases in Regional Multidiscplinary Tumor Board (MTB) dedicated to NETs (RENATEN MTB). Methods: This study is a retrospective observational study including patients aged 75 years and over, with a NET that has been diagnosed in an pathological laboratory or whose file has been discussed in a MTB (usual MTB or RENATEN MTB) between 2014 and 2017 in the Brittany area. Results: 51 patients with a median age of 79 years [75-92] have been included up until now, among whom 77% had digestive NET, 12% urological, 8% dermatological (Merkel tumor), 4% pulmonary, 2% gynecological and 2% NETs of unknown origin. Tumor grade was 1, 2, 3 and unkown in 20%, 14%, 37% and 29% respectively. Overall, 33% of the tumors were well differentiated and 63% were metastatic (synchronous metastases :78%). Only 20% of patients benefited from a geriatric oncology consultation to help the clinician in the therapeutic decision. File of 53% of patients has been discussed one time in a specialized RENATEN MTB and 57% in another MTB. No proof of discussion in MTB was found in 12%. The treatment proposed in the RENATEN MTB was effective in 85% of patients (2 patients died immediately after RENATEN MTB, 2 patients did not wish to be treated). Only 14% of patients received initial surgery, 10% radiotherapy and 41% chemotherapy. The overall survival of this cohort is 11.3 months [0.3 -89] (for grade 3, 7.9 months [0.8-21.7]). Conclusions: The rate of multidisciplinary meeting presentation has to be improved, as well as the geriatric oncology management. A cohort of more than 100 patients will be presented at the meeting and treatment response and survival data based on age class, tumor grade, histological subtypes and therapeutic strategy will be shown.

7500 Background: MPM median overall survival (OS) did not exceed 13 months with pemetrexed-platinum doublet, with virtually no surviving patients at 5 years. Vascular endothelial growth factor is a...

7505 Background: Surgical resection followed by adjuvant platinum-based CT is the standard of care in stages II and III of NSCLC. ERCC1 is considered as a molecular determinant of benefit to platin-based CT and is an independent good prognostic marker in resected NSCLC. EGFR mutations predict for erlotinib efficacy. We included ERCC1 IHC status and EGFR mutational status in a prospective randomized multicentric phase II/III customized adjuvant CT trial. Methods: Completely resected patients (pts) with non-squamous tumors, mediastinal lymph node dissection and pathological stage IIA, IIB or IIIA (N2 excluded) (6th TNM edition) were randomized either to a control arm (A) or a customized arm (B). Surgical blocks were centralized for biomarkers analyses. The control arm encompassed 4 cycles of standard dose cisplatin-pemetrexed (CP). In the experimental arm, EGFR mutated pts received erlotinib 150 mg for one year. ERCC1 negative pts received four cycles of CP. ERCC1 positive pts were closely monitored. The Fleming’s single stage phase II primary endpoint was feasibility (ie % of patients able to start therapy within 2 months of surgery and for which the biomarker’s status was readily available) (H0 64%, H180%, α 5% and β 95%). Results: 150 pts were randomized between May 2009 and July 2012, 74 in arm A and 76 in arm B. Most pts were male (61%), ≤ 60 years (51%), and smokers (91%). Pathological stage was IIA in 69 pt, IIB in 48 pt and IIIA in 32 pt. ERCC1 was positive in 38 pts (19 in each arm), EGFR mutation was identified in 10 pts (3 in arm A, 7 in arm B). In arm A, all pts received CP. In arm B, 7 pts received erlotinib, 53 pts received CP and 16 were followed-up. The median exposure time to erlotinib was 276 days (10-365). Out of 127 pts allocated to CP, 82% received the expected 4 cycles with a very good tolerability profile (no febrile neutropenia). The success rate was 80% (120 out of 150 pts). Conclusions: This adjuvant trial met its primary end point for its phase II component, demonstrating the feasibility of a national biology-driven trial in the adjuvant setting. Nevertheless the phase III was canceled due to the unexpected unreliability of the ERCC1 IHC read-out. Clinical trial information: NCT00775385.

7503 Background: EGFR tyrosine kinase activating mutations are present in 10-26% of NSCLC tumors and are associated with increased response to gefitinib and erlotinib. However, little is known about how the efficacy and safety profile of erlotinib compares with CT in EGFR-mutant Caucasian p. We have performed a prospective, randomized phase III study comparing erlotinib with platinum-based CT in chemonaive advanced NSCLC p with EGFR mutations. Methods: From February 2007 to January 2011, we screened 1,227 p for EGFR mutations, and 174 patients were randomly assigned to receive erlotinib or platinum-based CT. The primary endpoint was progression-free survival (PFS). Secondary endpoints included response, overall survival and toxicity profiles. Results: 153 p (76 CT, 77 erlotinib) are evaluable for the interim analysis. p characteristics CT arm: 16 males; median age, 64; never smokers, 56; PS 0, 26; PS 1, 41; adenocarcinoma, 67. p characteristics erlotinib arm: 25 males; median age, 65; never smokers, 54; P...

10556 Background: Activating mutations of the EGFR gene in lung adenocarcinoma have been associated with response to tyrosine kinase inhibitors. Therefore, a rapid, sensitive assay for mutation det...

7536 Background: Elderly pts is an heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and activity of ...

e18002 Background: Elderly patients (pts) are a heterogeneous population in which anticancer therapeutic decision is often difficult. The objective of this study was to evaluate the feasibility and...

7631 Background: The optimal strategy in advanced NSCLC with stable disease is not well known. There is no published study assessing an early change of chemotherapeutic drugs in these patients. This study was designed to evaluate the efficacy and safety of early modification of chemotherapy doublets in patients with advanced non small cell lung cancer with stable disease (SD). Methods: Patients with stage IV NSCLC and measurable disease were included in a randomized phase II trial comparing for patients with stable disease after 2 cycles of a platin (P)-gemcitabine doublet (P d1: 75 mg/m2, gemcitabine 1 250 mg/m2 d1, d8 every three weeks) two subsequent cycles of this doublet (arm A) to a switch to another doublet (arm B): paclitaxel 100 mg/m2 d1, d8, d15, gemcitabine 1 250 mg/m2 d1, d8, every four weeks. Results: Between October 2003 and august 2006, 228 patients (pts) were enrolled (187 males, 41 females), median age 57 y (30–70). Evaluation (EVA) 1 showed 11.8% not assessable patients (NA), 19.3% with objective responses (OR), 25.9% with progressive diseases. 98 patients (43%) had stable diseases. 87 patients were randomized in the study. 48.3% with PS0, 51.7% with PS1 and a majority of adenocarcinoma (62.1%). 41.4% had only one metastatic site. There were no differences between the two groups. Efficacy at eva 2 is depicted above. Overall survival (OS) was similar between the two arms: 9.8 months (m) [7.0 - 14.2] for arm A, 9.2 m [7.4 - 10.5] for arm B. TTP was 5.4 m in arm A and 5.7 in arm B. There were 1 grade III/IV haematological toxicities in arm A (1.2%) and 2 in arm B (2.4%). There were 4 grade III/IV non haematological toxicities in arm A (4.8%) and 6 in arm B (7.3%). Conclusions: The switch between the two regimen is feasible without any major toxicities. Despite higher response rate in favour of the switch strategy, OS and TTP are similar between the two arms. No significant financial relationships to disclose. [Table: see text]