3076 Tumor control of advanced pulmonary carcinoid tumors with somatostatin analogs: Experience at Gustave Roussy

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Abstracts

3074 POSTER Platinum-pemetrexed palliative chemotherapy in malignant pleural mesothelioma from Spanish BEMME database The Spanish Lung Cancer Group (SLCG)

3075 POSTER Association between clinical outcome of first EGFR-TKIs and T790M mutation in NSCLC patients harboring EGFR mutation with acquired resistance to EGFR-TKIs

J. Remon1 , N. Reguart2 , Y. Garcia3 , E. Nadal4 , R. Lopez-castro5 , R. Garcia-campelo6 , P. Martin-martorell7 , O. Juan8 , E. Olmedo9 , F. Trancho10 , M. Domine11 , S. Ponce12 , D. Cumplido13 , M. Majem14 , B. Massuti15 , R. Porta16 , D. Rodriguez-abreu17 , M. Provencio18 . 1 Hospital De Mataro, Oncology, Mataro, Spain; 2 Hospital Clinic I Provincial De Barcelona, Medical Oncology, Barcelona, Spain; 3 Hospital De Sabadell, Medical Oncology, Sabadell, Spain; 4 Institut Catala d’Oncologia l’Hospitalet, Ico, Medical Oncology, Barcelona, Spain; 5 Hospital Clinico Universitario De Valladolid, Medical Oncology, Valladolid, Spain; 6 Hospital Materno Infantil Teresa Herrera, Medical Oncology, A Coruna, Spain; 7 Hospital Clinico Universitario Valencia, Medical Oncology, Valencia, Spain; 8 Hospital Universitari I Politecnic La Fe, Medical Oncology, Valenica, Spain; 9 Hospital Ramon Y Cajal, Medical Oncology, Madrid, Spain; 10 Hospital Clinico San Carlos, Thoracic Surgery, Madrid, Spain; 11 Hospital Universitario Fundacion Jimenez Diaz, Medical Oncology, Madrid, Spain; 12 Hospital Universitario 12 De Octubre, Medical Oncology, Madrid, Spain; 13 Hospital De Torrevieja, Medical Oncology, Alicante, Spain; 14 Hospital De La Santa Creu I Sant Pau, Medical Oncology, Barcelona, Spain; 15 Hospital General Universitario De Alicante, Medical Oncology, Alicante, Spain; 16 Institut Catala d’Oncologia Girona, Ico, Medical Oncology, Girona, Spain; 17 Hospital Universitario Insular De Gran Canaria, Medical Oncology, Las Palmas De Gran Canaria, Spain; 18 Hospital Universitario Puerta De Hierro Majadahonda, Medical Oncology, Madrid, Spain

Y. Oya1 . 1 Aichi Cancer Center, Respiratory Disease, Nagoya, Japan

Background: Cisplatin and antifolate-based combination chemotherapy is the current standard first-line treatment for advanced and unresectable MPM patients with a median overall survival (OS) of 12 months and a response rate (RR) of 24% to 43%. The substitution of cisplatin by carboplatin is widespread by the perception of lesser toxicity. An expanded access program (EAP) reported similar RR and OS for carboplatinbased therapy compared with cisplatin plus pemetrexed. BEMME (Base Epidemiologica ´ Mesotelioma Maligno en Espana) ˜ is an observational and retrospective study sponsored by the SLCG that aimed to characterize the patient’s and tumor’s features as well as the treatment modalities outcomes of patients diagnosed with mesothelioma in Spain. Methods: Clinical records of patients with malignant pleural mesothelioma were retrospectively reviewed to collect epidemiological and survival data into an electronic and anonymous database. Thirty-five Spanish hospitals participated in the project and 538 MPM patients were included in the BEMME database. Here we present a descriptive analysis of MPM patients (stage III and IV) treated with platinum-palliative chemotherapy. Results: From January 2008 to December 2013, 297 of 538 patients (p) (55%) with MPM were treated with palliative chemotherapy. Most patients were males (79%), aged between 60−70 y (40%), and 60% had a performance status 1 at diagnosis. No exposure to asbestos was reported in 54% of patients. Epithelioid was the most frequent histological subtype (66%), followed by sarcomatoide (12%), biphasic (9%) and not specified (14%). In stage IV, the most frequent metastatic site was lung (35%). Among patients who received chemotherapy, 55% were treated with palliative intent and reached a disease control rate (CR+PR+SD) of 62%. Platinum plus pemetrexed was the most common schedule used as a palliative treatment, without differences in ORR according to platinumbased agent used (Cisplatin: 36% vs. Carboplatin: 32%). A total of 61 (21%) received maintenance. The median OS for all patients was 12.6 months (95% CI 10.8–14.3). OS in non-epithelioid histology was 7 months (95% CI 4.3−9) compared to epithelioid 15 months (95% CI 13.8−18, p < 0.001). Differences in OS according to platinum-drug received (Cisplatin vs. Carboplatin) were not statistically significant (15.2 months vs. 18 months, p = 0.32). Cisplatin outcome was independent of gender, asbestos exposure and histology. However, in carboplatin treated group, the benefit was significantly greater in epithelioid vs. non-epithelioid histology subtype (21 months 95% CI 14−42 vs. 7 months 95% CI 4.3-NA, p = 0.002). Conclusions: Disease control rate and survival of Spanish MPM patients treated with palliative chemotherapy does not differ according to platinumagent used. Carboplatin might have a lower magnitude of benefit in nonepithelioid histology. No conflict of interest.

Background: Patients with NSCLC with EGFR-activating mutations initially respond to EGFR-TKIs. However, clinical efficacy is limited by acquired resistance, and the secondary EGFR T790M mutation accounts for approximately half of acquired resistances to EGFR-TKI. Third generation EGFR-TKIs that specifically targets T790M mutation was developed for overcoming the acquired resistance. The clinicopathologic features related to T790M mutation in patients with acquired resistance to EGFR-TKIs remains unknown. Methods: We investigated 120 NSCLC patients harboring EGFR-activating mutations who underwent re-biopsy after acquired resistance to EGFRTKIs from January 2005 to April 2015. Patient characteristic, progression pattern at the re-biopsy, and initial response on first EGFR-TKIs were retrospectively compared in patients with and without T790M. Results: Of the 120 patients had acquired resistance to EGFR-TKIs, Median age was 64(range: 35−84),47(39.1%)was male. 105 patients received gefitinib and 13 erlotinib and 2 afatinib as first EGFR-TKIs.At the time of re-biopsy, 63 (52.5%) had T790M mutation. Median PFS on first EGFR-TKIs in patients with T790M mutation was significantly longer than those without T790M mutation (430 days vs 236 days, p = 0.02). In 63 of 120 patients who underwent re-biopsy at RECIST-PD of first EGFR-TKIs, the patients with T790M mutation had significantly more local progression and less systemic progression than those without T790M (T790M+: local 70.9%, systemic 29.0%, T790M−: local 40.6%, systemic 59.3%, p = 0.01) Conclusions: The emergence of T790M mutation in patients who had acquired resistance to EGFR-TKIs is significantly related with longer PFS on first EGFR-TKIs and local progression at the time of re-biopsy. No conflict of interest. 3076 POSTER Tumor control of advanced pulmonary carcinoid tumors with somatostatin analogs: Experience at Gustave Roussy I. Sullivan1 , E. Baudin2 , J. Guigay1 , J.Y. Scoazec3 , S. Leboulleux2 , A. Berdelou2 , M. Ducreux1 , D. Malka1 , C. Caramella4 , B. Besse1 , D. Planchard1 . 1 Gustave Roussy, Medical Oncology, Villejuif, France; 2 Gustave Roussy, Nuclear Medicine and Endocrine Oncology, Villejuif, France; 3 Gustave Roussy, Pathology, Villejuif, France; 4 Gustave Roussy, Radiology, Villejuif, France Background: Pulmonary carcinoids are rare neuroendocrine tumors (puNETs) of the lung with no standard therapeutic option. Antitumor control benefit of somatostatin analogs (SSAs) has been demonstrated in gastroeneropancreatic (GEP)-NETs, but only a few data have been published in puNETs. Material and Methods: Data from advanced puNETs patients treated with SSAs in monotherapy between 1986 and 2014 at Gustave Roussy were retrospectively collected. Demographical, clinical and tumor-related features were recorded. Patients had a tumor evaluation by CT-scan and/or MRI every 3 months. Progression-free survival (PFS) and Overall survival (OS) were estimated using Kaplan–Meier. Response rate and toxicity were assessed according to RECIST (v1.0 until 2008 and v1.1 since 2009) and NCI.CTC v4.03 criteria respectively. Results: Sixty-one metastatic patients with a median follow-up of 5.8 yrs (0.4–13.0 yrs) were included, with a median age of 55 yrs (13−84 yrs), 55.7% were male, 29% current or former smokers, and 95% had PS 1. At diagnosis, 20 patients were classified as typical carcinoids (TCs) and 41 as atypical carcinoids (ACs) according to 2004 WHO classification. Before SSAs initiation, 49 patients (80%) showed uptake at somatostatin receptor scintigraphy (SRS) (grade 2) and 29 (52%) showed hormonerelated symptoms. The majority of patients (75.4%) presented at least two metastatic sites, liver being the most frequent one (80.3%). Fortysix (75%) patients received SSAs as first-line therapy: 32 patients (70%) for disease progression and 14 patients (30%) for symptomatic carcinoid syndrome. The median duration of SSAs was 13.7 months (3.0–155.1). Overall, median PFS (mPFS) and OS (mOS) were 17.4 [95% CI=8.7– 26.0] and 58.4 months [44.2–102.7], respectively. Best response was stable disease (SD) for 43 patients (70.5%) and progression disease (PD) for 14 patients (23%). All PD were ACs. The number of events and deaths was 46 (75%) and 29 (48%), respectively. mPFS was 24.8 months [10.1–36.3] for the TCs and 12.8 months [6.2–26.0] for the ACs patients (p = 0.32). mPFS was significantly longer in functional puNETs with a mPFS of 28.7 months [13.2–55.6] vs. 8.7 months [5.8–21.2] in non-functional tumors

Abstracts (p = 0.01). The most common adverse event was grade 1 diarrhea in 43% of patients. Only one grade 3 (abdominal pain) was reported with a consequent withdrawal of treatment. Conclusion: In the real-world setting, somatostatin analogs are safe and potentially effective for the antitumor control of puNETs. Our results suggest that patients with typical carcinoids and functional tumors seem to benefit most from SSAs therapy. No conflict of interest. 3077 POSTER 65 plus: A randomized phase III trial of Pemetrexed and Bevacizumab vs. Pemetrexed, Bevacizumab and Carboplatin as 1st line treatment for elderly patients with advanced non-squamous, non-small cell lung cancer (NSCLC) − a subgroup analysis of age and gender W. Schuette1 , B. Nieman1 , C.P. Schneider2 , W. Engel-Riedel3 , C. Schumann4 , M. Kohlhaeufl5 , M. Serke6 , G. Hoeffken7 , C. Kortsik8 , M. Reck9 . 1 Krankenhaus Martha-Maria Halle-Doelau, Klinik fuer Innere Medizin II, Halle, Germany; 2 Zentralklinik Bad Berka, Pneumologie, Bad Berka, Germany; 3 Kliniken der Stadt Koeln, Krankenhaus Merheim-Lungenklinik, Koeln, Germany; 4 Klinikum Kempten, Klinik fuer Pneumologie, Thoraxonkologie, Schlaf, und Beatmungsmedizin, Kempten-Oberallgaeu, Germany; 5 Klinik Schillerhoehe Gerlingen, Zentrum fuer Pneumologie u.Thoraxchirurgie, Gerlingen, Germany; 6 Lungenklinik Hemer, Pneumologie, Hemer, Germany; 7 Fachkrankenhaus Coswig, Zentrum fuer Pneumologie, Thorax, u. Gefaeßchirurgie, Coswig, Germany; 8 Katholisches Klinikum Mainz, Klinik fur ¨ Pneumologie, Beatmungs, und Schlafmedizin, Mainz, Germany; 9 Lungenklinik Grosshansdorf, Zentrum fur ¨ Pneumologie und Thoraxchirurgie, Grosshansdorf, Germany Background: Pemetrexed (P) and Bevacizumab (B) are efficacious drugs for treatment of non-squamous NSCLC. In this trial the benefit of combining PB with Carboplatin (C) was investigated in elderly patients (pts) 65 years with advanced NSCLC. Methods: In this German multicenter (27 centers), open-label phase III trial pts with stage IIIb/IV non-squamous NSCLC were recruited. Pts were randomized 1:1 to P (500 mg/m2 ) + B (7.5 mg/kg) or P+B+C (AUC5) d1 q3 wks for 4 to 6 cycles followed by maintenance therapy with B or P+B. The primary endpoint was progression-free survival (PFS), while secondary endpoints included among others overall survival (OS) too. A retrospective subgroup analysis for the predefined age and gender was performed. Results: 271 pts were enrolled from Sep 2009 to Jan 2012, the ITT population consists of 253 evaluable pts. (PB 119 pts, PBC 134 pts). As presented earlier, Median PFS was 4.8 mo (PB) versus 6.8 mo (PBC), respectively. Treatment comparison for ECOG performance status (PS) 0−1 group (PB 113 pts, PBC 127 pts): p = 0.0290 (Wilcoxon test), hazard ratio (HR) =1.353 (95% CI 1.030–1.777). Median OS was 11.6 mo (PB) vs. 14.4 mo (PBC), respectively. Median OS time was 11.6 mo in PB vs. 14.4 mo in PBC. Treatment comparison ECOG PS 0−1: p = 0.2739 (Wilcoxon test), HR = 1.102 (95% CI 0.793–1.532)[1]. In the new subgroup analysis the overall survival benefit for PBC was significant in the subgroup <70 years: p = 0.0039 (Wilcoxon test), HR = 2.039 (95% CI 1.150–3.616) as well as PFS for subgroup <70: p = 0.0271 (Wilcoxon test), HR = 1.628 (95% CI 0.994–2.667). Whereas for the subgroups of patients aged 70−75 (OS: p = 0.2445, HR = 0.667 (95% CI 0.397–1.120; PFS: p = 0.7391, HR = 1.178 (95% CI 0.786–1.766)) or >70 years (OS: p = 0.6139, HR = 1.174 (95% CI 0.632–2.183; PFS: p = 0.3463, HR = 1.337 (95% CI 0.764–2.340)), significant differences between treatment arms were not observed. No difference between gender was observed: OS p = 0.3869 (Wilcoxon test), HR = 1.091 (95% CI 0.794–1.499); PFS p = 0.0583, HR = 1.285 (95% CI 0.985–1.677). Conclusions: While younger patients (<70 y/o) significantly benefit from the addition of carboplatin to Bevacizumab and Pemetrexed this benefit cannot be shown in patients being older than 70 years, independent of the ECOG PS. No influence of the gender to PFS or OS was observed. [1] Schuette et al; 65 plus: A randomized phase III trial of pemetrexed and bevacizumab versus pemetrexed, bevacizumab, and carboplatin as firstline treatment for elderly patients with advanced nonsquamous, non-small cell lung cancer (NSCLC). J Clin Oncol 31, 2013 (suppl; abstr 8013) Conflict of interest: Advisory Board: Amgen, AstraZeneca, Lilly, Roche,.

S623 3078 POSTER Updated results and efficacy analysis according to epidermal growth factor receptor (EGFR) mutation subtypes and metastatic sites for the phase II trial of gefitinib in combination with carboplatin plus S1 A. Tamiya1 , M. Tamiya2 , T. Shiroyama2 , T. Tsuji1 , N. Morishita2 , N. Omachi1 , N. Okamoto2 , S. Hidekazu2 , K. Okishio3 , T. Hirashima2 , S. Atagi3 . 1 Kinki Chuo Chest Medical Center, internal medicine, Sakai, Japan; 2 Osaka Prefectural Medical Center for Respiratory and Allergic Diseases, Thoracic Oncology, Habikino, Japan; 3 Kinki Chuo Chest Medical Center, Thoracic Oncology, Sakai, Japan Background: Good efficacy and survival was observed in patients with advanced non-small cell lung cancer harboring epidermal growth factor receptor (EGFR) mutation. And the phase II study treated with gefitinib plus carboplatin and S1 previously demonstrated the good efficacy in terms of progression free survival (PFS) and response rate (RR) as the firstline treatment of advanced NSCLC harboring activating EGFR mutations (Tamiya A, et al. Med Oncol. 2015). Material and Methods: This trial was multi-center, open rabel, single arm trial. All patients had advanced non-small cell lung cancer (Stage IIIB/IV) harboring activating mutations. A total of 35 patients received carboplatin on day 1 plus oral S1 on days 1−14 and gefitinib daily. Updated results and subgroup analysis according to EGFR mutations and metastatic sites are presented. Results: All patients had lung adenocarcinoma with activating EGFR mutations, namely, deletion (exon 19; n = 22), L858R (exon 21; n = 12), and T790M/L858R (exons 20 and 21; n = 1). Almost all patients had stage IV disease. The updated analysis revealed response rate of 85.7%, a median PFS of 17.6 months (95% CI: 13.4–23.0 months), and a median overall survival (OS) was not reached (95% CI: 27.8 months −). Response rate and median PFS and median OS were 90.9%, 18.7 months (95% CI: 15.5–28.4 months) and not reached (95% CI: 27.8 months −) in the exon 19 del+ arm, and 83.3%, 13.4 months (95% CI: 6.2–18.5 months), and 27.9 months (95% CI: 10.1–32.4 months) in the exon 21 (L858R) arm. The significant difference of OS were observed between with or without the bone metastasis (P = 0.0021), and there were no significant difference of PFS and OS in other metastatic site. The common toxicities related to gefitinib were skin rash, elevated transaminase and diarrhea. And the common toxicity in the present trial was neutropenia. No interstitial lung disease or treatment-related deaths occurred. Conclusions: This triplet chemotherapy (gefitinib in combination with carboplatin plus S1) showed good efficacy and prolonged PFS. And this analysis showed the different efficacy in terms of PFS and OS between EGFR mutation subtypes and the different efficacy in terms of OS between the presents of bone metastasis. Conflict of interest: Ownership: none. Advisory Board: none. Board of Directors: none. Corporate-sponsored Research: Merck Serono,. Boehringer Ingelheim,. AstraZeneca,. Taiho Pharmaceutical,. Yakult Pharmaceutical Industry,. Eli Lilly. Other Substantive Relationships: none. 3079 POSTER Randomized phase II trial of amrubicin plus irinotecan versus cisplatin plus irinotecan in chemo-na¨ıve patients with extensivedisease small-cell lung cancer: Results of the Japan Multinational Trial Organization (JMTO) LC 08−01 A. Tamiya1 , H. Yoshioka2 , T. Nishimura3 , Y. Iwamoto4 , Y.H. Kim5 , K. Tomii6 , N. Katakami7 , K. Komuta8 , M. Nishikawa9 , K. Yamaki10 , A. Gemma11 , M. Kawahara12 , S. Atagi13 , T. Yamanaka14 , C. Miyakoshi15 , T. Mio16 . 1 Kinki Chuo Chest Medical Center, internal medicine, Sakai, Japan; 2 Kurashiki Central Hospital, Respiratory Medicine, Kurashiki, Japan; 3 Kyoto Katsura Hospital, Respiratory Medicine, Kyoto, Japan; 4 Hiroshima City Hiroshima Citizens Hospital, Respiratory Medicine, Hiroshima, Japan; 5 Kyoto University Hospital, Respiratory Medicine, Kyoto, Japan; 6 Kobe City Medical Center General Hospital, Respiratory Medicine, Kobe, Japan; 7 Institute of Biomedical Research and Innovation, Integrated Oncology, Kobe, Japan; 8 Osaka Police Hospital, Respiratory Medicine, Osaka, Japan; 9 Fujisawa City Hospital, Respiratory Medicine, Fujisawa, Japan; 10 Ichinomiya Nishi Hospital, Internal Medicine, Ichinomiya, Japan; 11 Nippon Medical School Hospital, Division of Pulmonary Medicine − Infectious Diseases, and Oncology Department of Internal Medicine, Tokyo, Japan; 12 Otemae Hospital, Respiratory Medicine, Osaka, Japan; 13 Kinki Chuo Chest Medical Center, Thoracic Oncology, Sakai, Japan; 14 Yokohama City University, Biostatistics, Yokohama, Japan; 15 Kobe City Medical Center General Hospital, Pediatrics and Neonatology, Kobe, Japan; 16 National Hospital Organization Kyoto Medical Center, Respiratory Medicine, Kyoto, Japan Background: Clinical efficacy of topoisomerase I inhibitor amrubicin has been demonstrated in patients with small-cell lung cancer (SCLC) but