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L. Bonanno



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    MA 01 - SCLC: Research Perspectives (ID 650)

    • Event: WCLC 2017
    • Type: Mini Oral
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      MA 01.07 - Lanreotide Maintenance in SCLC Expressing Somatostatine Receptors: Efficacy Results of Multicenter Randomized G04.2011 Trial (ID 8480)

      11:40 - 11:45  |  Author(s): L. Bonanno

      • Abstract
      • Presentation
      • Slides

      Background:
      SCLC is featured by both a rapid response and progression during/after standard upfront therapy. Thus, maintenance strategies emerged as potential treatment opportunities, although to date all drugs failed to significantly improve prognosis. SCLC cells harbor a neuroendocrine phenotype, frequently expressing somatostatine (SST) receptors. This study aimed to investigate the efficacy of somatostatine (SST) analogue Lanreotide (LAN) as a maintenance strategy for SCLC patients (pts) after response to standard upfront treatment.

      Method:
      A multicentre, randomized, open-label, no-profit national trial was conducted, randomizing (1:1) SCLC (limited/extended disease, L/ED) pts expressing SST receptors (by SST receptor scintigraphy) with objective response (CR or PR) after upfront platinum-based chemotherapy plus/minus radiotherapy to receive maintenance LAN 120 mg subcutaneously every 28 days, up to progressive disease (PD) for 1 year (Arm A), versus observation (Arm B). Primary end-point was 1-year Progression-Free Survival (PFS). Primary intention-to-treat (ITT) analysis was planned (power: 80%; 2-tailed alpha-error: 5%) after 47 PFS events.

      Result:
      Seventy-one pts (median age 66 [37-82]; male/female 72/28%; L/ED 39/61%; ECOG-PS 0-1/2 97/3%; previous best response CR/PR 6/94%) were randomized in 9 Italian centers. Median time from diagnosis and end-of-1[st] line to inclusion was 5.7 months (3-160) and 30 days (0-119), respectively. Median number of LAN doses and treatment duration (Arm A) was 4 (1-12) and 83 days (1-392), respectively. With a median follow-up of 9.4 months and 62 events, median PFS was 3.6 (95% CI 3.2-3.9) versus 2.3 months (95% CI 1.7-2.9), for Arm A and B (log-rank p=0.11; HR 1.51, 95% CI 0.90-2.50), with a 1-year PFS of 10.3% versus 7.3%, respectively. At the cox-proportional multivariate modelling, stage (ED versus LD, HR 2.88 [95% CI 1.64-5.04, p<0.0001) and treatment arm (B versus A, HR 1.63 [95% CI 0.97-2.72], p=0.06) were independent predictors for PFS. Median PFS of arm A and B was 7.0 [95% CI <1-13.5] and 3.8 months [95% CI <1-8.6] in LD pts (p=0.21), and 3.0 (95% CI 2.2-3.8) and 2.2 (95% 1.7-2.7) in ED pts (p=0.19). Median OS was 9.5 (95% CI 4.8-14.3) and 4.7 months (95% CI 1.7-16.6), for Arm A and B (log-rank p=0.47), respectively. LAN was well-tolerated: serious treatment-related adverse events were grade 3 abdominal pain and electrolyte disorder in overall 2 pts.

      Conclusion:
      Although the primary end-point was not met, the overall efficacy of LAN as a maintenance strategy after response to standard upfront treatment for SCLC deserves future investigations, particularly in pts with LD.

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    P1.01 - Advanced NSCLC (ID 757)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P1.01-015 - Crizotinib in ROS1 Rearranged or MET Deregulated Non-Small-Cell Lung Cancer (NSCLC): Final Results of the METROS Trial (ID 9454)

      09:30 - 09:30  |  Author(s): L. Bonanno

      • Abstract

      Background:
      Crizotinib is the standard of care in NSCLC with ALK rearrangement. Recent data showed that the drug is dramatically effective in patients with ROS1 rearrangement (ROS1[+]), with promising activity also in individuals with MET exon 14 mutations (MET[Ex14]) or MET amplification (MET[FISH+]).

      Method:
      The METROS is an Italian multicenter prospective phase II trial designed to assess the efficacy and safety of crizotinib in ROS1[+ ]or MET[Ex1][4 ]or MET[FISH][+ ]advanced NSCLC patients who failed at least 1 standard chemotherapy regimen. The co-primary end-point was response rate (RR) in cohort A (ROS1+: centrally confirmed ROS1 rearrangement) and cohort B (MET+: centrally confirmed MET[FISH][+ ]defined as ratio MET/CEP7 >2.2 or locally confirmed MET[Ex1][4]). Eligible patients received crizotinib at the standard dose of 250 mg BID orally.

      Result:
      At the data cut-off of April 30[th], 2017, both cohorts completed accrual. Among 498 screened patients, 52 accounted for the intent-to-treat population (ITT) and received at least 1 dose of crizotinib. Among them, 26 resulted ROS1[+], 16 MET[FISH][+] and 10 MET[Ex1][4]. Notably, 3 MET[Ex1][4] cases had concurrent KRAS mutation and 1 had concurrent MET gene amplification. No concomitant driver event was detected in the ROS1 cohort. Cohort A included individuals with adenocarcinoma, median age of 55 years (range 29-86), predominantly female (61%) and never smokers (54%). Cohort B included older subjects (median age 68, range 39-78), predominantly male (65%), current/former smokers (77%) and with adenocarcinoma (92%). In both cohorts, the vast majority of patients (85%) presented > 2 metastatic sites and crizotinib was mainly offered as second line treatment (74%). Time from end of first line therapy to crizotinib was 4.1 and 1.6 months for cohort A and B, respectively. In ITT population RR, median progression free-survival (PFS) and overall survival (OS) were 61.5%, 17.2 months and not reached in cohort A and 26.9%, 3.1 months and 5.3 months in cohort B, respectively. For cohort B, responses were observed in both MET[FISH][+] and MET[Ex1][4] (25% and 30%, respectively), with evidence of rapid progression in patients carrying MET[Ex1][4][/KRAS]. At present, for 2 MET+ patients assessment is pending. Therapy was generally well tolerated with no unexpected adverse event.

      Conclusion:
      The METROS is the first prospective trial specifically conducted in ROS1+ or MET+ deregulated NSCLC. The study confirms remarkable efficacy of crizotinib in ROS1[+] NSCLC. Responses observed in the MET cohort were of short duration confirming aggressiveness of the disease and the urgent needs for innovative therapies.