Abstract Book

ESTRO 37

S388

3 Royal Wolverhampton NHS Trust, Clinical Oncology, Wolverhampton, United Kingdom 4 The Christie Hospital Foundation Trust, MAHSC-CTU, Manchester, United Kingdom 5 The University of Manchester, Cancer Research, Manchester, United Kingdom 6 The Christie NHS Foundation Trust, Clinical, Manchester, United Kingdom 7 University of Manchester, Radiology, Manchester, United Kingdom 8 The Christie NHS Foundation Trust, Diagnostic radiology and nuclear medicine, Manchester, United Kingdom 9 The Christie NHS Foundation Trust, Diagnostic Radiology, Manchester, United Kingdom 10 The Christie NHS Foundation Trust, MAHSC-CTU, Manchester, United Kingdom 11 The University of Manchester and The Christie NHS Foundation Trust, Radiation, Manchester, United Kingdom Purpose or Objective The RAS/RAF/MEK/ERK signalling pathway has a pivotal role in cancer proliferation and modulating treatment response. Selumetinib (AZD6244/ ARRY-142886) an inhibitor of MEK, has been shown to enhance the effect of radiotherapy (RT) in preclinical studies. Material and Methods This single-arm, single-centre, open-label phase I trial, recruited patients with stage III non-small cell lung cancer (NSCLC) unsuitable for concurrent chemo- radiotherapy or stage IV with dominant thoracic symptoms. Enrolment to the dose-finding stage used a Fibonacci 3+3 design (maximum number=18) followed by recruitment of an expanded cohort (n=15). Oral selumetinib was administered at a starting dose of 50mg twice daily commencing 7 days before RT, then in combination with thoracic radiotherapy (TRT) for 6-6.5 weeks (60-66Gy in 30-33 fractions). The primary objective was to determine the recommended Phase 2 dose. Results From 06/10-02/15, 21 patients were enrolled. Median age 63 years (range 50-73). M:F ratio 12(57%):9(43%). ECOG PS 0:1, 7(33%):14(67%). Stage III 16(76%):IV 5(24%). Mean GTV 64cm3 (range 0.8–223.73). In the dose- finding stage, 2 out of a total of 6 patients experienced dose-limiting toxicities (DLT) but only one DLT (G3 diarrhoea) was treatment-related. Despite meeting the pre-defined criteria for escalation, the trial management group elected to treat the expanded cohort (n=15) at the starting dose. All 21 received induction chemotherapy and completed TRT as planned. Compliance to selumetinib was >80%. The most common adverse events are listed in table 1. There were 2 survivors (24 & 26 months) at analysis. The 1-year survival was 38%, stage III 44% vs stage IV 20%, 2-year survival was 24%, stage III 31% vs stage IV 0%. The main cause of disease progression was distant metastases in 10/21 (48%).

Conclusion The combination of thoracic radiotherapy and selumetinib is feasible and associated with an acceptable toxicity profile. However our results, based on 21 patients, do not suggest this combination should be pursued in a subsequent phase 2 trial. PO-0754 Safe inhomogeneus RT dose escalation in locally advanced NSCLC, -interim results from NARLAL2 T. Schytte 1 , T. Nielsen 2 , D. Moeller 3 , L. Hoffmann 3 , A. Khalil 3 , M. Knap 3 , M. Lund 4 , C. Nyhus 4 , T. Hansen 4 , W. Ottosson 5 , S. Borissova 5 , A. Appelt 6 , C. Brimk 2 , O. Hansen 1 1 Odense University Hospital, Department of Oncology, Odense, Denmark 2 Odense University Hospital, Laboratory of Radiation therapy, Odense, Denmark 3 Aarhus University Hospital, Department of Oncology, Aarhus, Denmark 4 Vejle Hospital, Department of Oncology, Vejle, Denmark 5 Herlev Hospital, Department of Oncology, Herlev, Denmark 6 St James Hospital, Institute of Pathology and Cancer, Leeds, United Kingdom Purpose or Objective Despite curative intend, the outcome of locally advanced non-small cell lung cancer (LA-NSCLC) remains poor with 2 years survival on 50% in clinical trials. The poor survival is affected by co-morbidity, distant metastasis, but also caused by the lack of loco-regional control. Radiotherapy (RT) dose escalation may be the answer to improve loco- regional control and there by survival. Unfortunately, it has not been the case in randomized dose-escalations trials, one study had even poorer survival in the experimental arm (RTOG 0617). When designing new dose escalations trials for NSCLC it is therefore of importance to ensure that the experimental treatment is not too toxic compared to standard treatment.