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N. Steele



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    P1.02 - Poster Session with Presenters Present (ID 454)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-007 - Alk Translocated NSCLC in the West of Scotland: Patient Demographics and Outcomes (ID 4199)

      14:30 - 14:30  |  Author(s): N. Steele

      • Abstract

      Background:
      A translocation in the anaplastic lymphoma kinase gene is found in 3-5% of non-small cell lung cancer (NSCLC). Patients with this mutation (ALK+) have shown marked responses to the tyrosine kinase inhibitor crizotinib. Second line Crizotinib has been available in Scotland since October 2013 for patients with ALK+ NSCLC. Since January 2014, reflex testing at diagnosis of all non-squamous NSCLC has been carried out in the West of Scotland (WoS) regardless of stage. Here we present the demographics of an Alk +ve cohort from an unselected Scottish NSCLC population and their clinical outcomes.

      Methods:
      Details of patients with Alk+ NSCLC were obtained from the regional molecular genetics laboratory. 60 patients with NSCLC from WoS tested ALK+ between 1st January 2014 and 30[th] June 2016. Patient records were reviewed retrospectively.

      Results:
      Median laboratory turnaround for alk testing was 21 days in 2014, 14 days in 2015 and 13 days in 2016. 3 (5%) patients were under 50 years, 8 (13%) 50-60 years, 23 (38%) 60-70 years, 17 (28%) 70-80 years and 9 (15%) patients were > 80 years old at time of testing. Median age was 69. 55% were male and 45% female. 67% were current or ex smokers. Only 22% were never-smokers. The majority (82%) had stage 3 or 4 disease at diagnosis. Only 39% (17/38) of patients with stage 4 ALK+ NSCLC were well enough to receive chemotherapy and 4 of these (24%) did not complete all planned cycles. 10 patients have received crizotinib so far. Median number of cycles is 3 overall (range 1-9). Where documented, reasons for discontinuation were disease progression or death from NSCLC (4), sudden death not related to NSCLC (2), intercurrent illness (2) and pneumonitis (1) . 3 patients continue on crizotinib as of June 2016. Of the 13 patients who have received crizotinib, 3 have had a PR, 4 SD 2 PD and 4 NE. Updated outcomes will be presented.

      Conclusion:
      A high quality reflex ALK testing service is being delivered in WoS with clinically acceptable turnaround times. Our ALK+ patients do not entirely reflect the literature and are frequently elderly, current or ex-smokers with advanced and aggressive disease. This may reflect the unselected nature of this population. Many Alk+ patients were too unwell to receive chemotherapy or tolerated it poorly and did not have the opportunity to access an alk inhibitor. First line Alk inhibitors may improve outcomes for this group of patients.

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    P1.07 - Poster Session with Presenters Present (ID 459)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      P1.07-015 - STOMP: A UK National Cancer Research Network Randomised, Double Blind, Multicentre Phase II Trial of Olaparib as Maintenance Therapy in SCLC (ID 4269)

      14:30 - 14:30  |  Author(s): N. Steele

      • Abstract

      Background:
      STOMP (ISRCTN 73164486, CRUK/10/037, EudraCT 2010-021165-76) is a randomised, double-blind, placebo-controlled phase II trial to evaluate activity and safety of the PARP inhibitor olaparib (AstraZeneca) as maintenance treatment for patients with chemo-responsive small cell lung cancer (SCLC). Two schedules of olaparib oral tablets were investigated: 300mg twice daily (bd) or 200mg three times daily (tds).

      Methods:
      Eligible patients had pathologically confirmed SCLC with response to first line chemotherapy or chemo-radiotherapy. Patients were stratified by metastasis-status and prior radiotherapy and randomised in a 2:2:1:1 ratio to: olaparib tds, olaparib bd, placebo tds or placebo bd. Placebo arms were pooled for analyses. Primary outcome was progression-free survival (PFS). There is 80% power to detect a difference of 3 months in PFS (from 4.8 months) between treatments based on a one-sided 5% significance level. Key secondary outcome measures were overall survival (OS), adverse events (AEs) and quality of life.

      Results:
      Between November 2013 and December 2015, 220 UK patients were randomised. Arms were well balanced for stratification factors of prior radiotherapy (89% Yes) and metastasis status (66% M1) as well as sex (46% M) and age (median=64, range 42-89). Median follow-up for 31 event-free patients was 14 months (range 0–24). Median PFS was 2.6 (90%CI 1.8, 3.7), 3.6 (90%CI 3.1, 6.0) and 3.6 (90%CI 3.1, 4.7) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in PFS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.87; 90% CI 0.64, 1.18; stratified logrank p=0.29) or the tds arm (0.89; 90% CI 0.67, 1.20; p=0.43). Median OS was 8.9 (90%CI 7.0, 11.9), 9.9 (90%CI 7.6, 12.9) and 9.0 (90%CI 6.6, 11.8) months in the placebo, olaparib bd and tds arms, respectively. There was no significant difference in OS between olaparib and placebo for either the bd (Cox-Adjusted HR 0.97; 90% CI 0.69, 1.37; stratified logrank p=0.73) or the tds arm (1.05; 90% CI 0.76, 1.46; p=0.73). The most common AEs on olaparib were fatigue, nausea, anaemia, vomiting and anorexia. 68 patients discontinued treatment citing AEs (17 placebo, 26 olaparib bd, 25 olaparib tds).

      Conclusion:
      There is no evidence that either the bd or tds regimen for olaparib improves PFS or OS in an unselected population. The AE profile for olaparib in SCLC is similar to that observed in other studies.

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    P3.02c - Poster Session with Presenters Present (ID 472)

    • Event: WCLC 2016
    • Type: Poster Presenters Present
    • Track: Advanced NSCLC
    • Presentations: 1
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      P3.02c-003 - TAX-TORC: The Novel Combination of Weekly Paclitaxel and the Dual mTORC1/2 Inhibitor AZD2014 for the Treatment of Squamous NSCLC (ID 4803)

      14:30 - 14:30  |  Author(s): N. Steele

      • Abstract
      • Slides

      Background:
      The dual mTORC1/2 inhibitor AZD2014 has multiple effects on cell growth, apoptosis, angiogenesis and metabolism in cancer cells. AZD2014 increases the efficacy of paclitaxel in preclinical models, including patient derived xenografts. These data and clinical responses in the dose escalation arm of the TAX-TORC study led to an expansion cohort of 40 patients with squamous non-small cell lung cancer (sqNSCLC).

      Methods:
      Patients, of ECOG performance status 0-1, with sqNSCLC who had received at least one line of platinum-based chemotherapy were eligible for the study. Paclitaxel was dosed once weekly at 80mg/m[2], 6 weeks out of 7. AZD2014 was dosed BD, 3 days per week starting with the paclitaxel dosing. The cohort was started at 50mg AZD2014 BD.

      Results:
      Thirty-two patients have been treated, 24 male/8 female with median age 68 years. The median number of previous treatments was 1 with 6/32 (19%) having received a prior taxane (docetaxel or paclitaxel). Analysis of data from the first 17 patients, by the safety review committee, showed that fatigue, skin rash and diarrhoea were the most common toxicities in 59%, 47% and 41% patients respectively. The majority of toxicities were CTCAE grades 1 or 2 (112/123, 91%) and reversible with AZD2014 interruption or reduction. However, there were 9 grade 3 and 4 toxicities and 2 incidences of grade 5 respiratory infection. There were 2/17 (12%) responses though patients often stopped early due to toxicity. Following the safety review, the dose of AZD2014 was reduced to 25mg BD which is a pharmacodynamically active dose associated with fewer toxicities. Fifteen additional patients have subsequently been treated at this lower dose. Their most common toxicities were anaemia, alopecia and fatigue in 47%, 47% and 40% patients respectively. There have been no grade 5 events and only 8/78 (10%) grade 3 or 4 toxicities. The response rate in this cohort is 5/15 (33%) and recruitment is ongoing. Archival samples and circulating free DNA at baseline are being assessed with targeted next generation sequencing to explore putative predictive biomarkers for response and resistance.

      Conclusion:
      We have established a tolerable dose and schedule for the combination of weekly paclitaxel and AZD2014. The promising response rate of 33% in previously treated sqNCSLC patients warrants further investigation. The study is supported by AstraZeneca, Cancer Research UK, Experimental Cancer Medicine Centre and NIHR Biomedical Research Centre Initiatives.

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