Virtual Library

 x 
My Library Virtual Library FAQ

Start Your Search

C. Faivre-Finn



Author of

  • +

    MO07 - NSCLC - Targeted Therapies II (ID 114)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MO07.11 - A randomised placebo-controlled multicentre phase II trial of erlotinib plus whole brain radiotherapy for patients with advanced non-small cell lung cancer with multiple brain metastases (TACTIC) (ID 2305)

      17:15 - 17:20  |  Author(s): C. Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Background
      Median survival of non-small cell lung cancer (NSCLC) patients with brain metastases is poor. We examined concurrent erlotinib and whole brain radiotherapy (WBRT) followed by maintenance erlotinib in patients with untreated brain metastases, given the potential radiosensitising properties of erlotinib and its direct effect on brain metastases and systemic activity.

      Methods
      Eighty NSCLC patients with KPS≥70 and multiple brain metastasis were randomised to placebo (n=40) or erlotinib (100mg, n=40) given concurrently with WBRT (20 Gy in 5 fractions). Following WBRT, patients continued with placebo or erlotinib (150mg) until disease progression. The primary end-point was neurological progression-free survival (nPFS).

      Results
      Fifteen patients (37.5%) from each arm were alive and without neurological progression 2 months after WBRT. Median nPFS was 1.6 months in both arms; nPFS HR 0.95 (95% CI, 0.59-1.54; p=0.84). Median overall survival (OS) was 2.9 and 3.4 months in the placebo and erlotinib arms; HR 0.95 (95% CI, 0.58-1.55; p =0.83). The frequency of EGFR mutations was low with only 1 out of 35 (3%) patients with available samples had activating EGFR-mutations. Grade 3/4 adverse event rates were similar between the two groups (70% in each arm), except for rash 20% (erlotinib) vs. 5% (placebo), and fatigue 17% vs. 35%. No significant QoL differences were found.

      Conclusion
      Our study showed no advantage in nPFS or OS for concurrent erlotinib and WBRT followed by maintenance erlotinib in patients with predominantly EGFR wild-type NSCLC and multiple brain metastases. Future studies should focus on the role of erlotinib with or without WBRT in patients with EGFR mutations.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MO23 - Radiotherapy II: Lung Toxicity, Target Definition and Quality Assurance (ID 107)

    • Event: WCLC 2013
    • Type: Mini Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 2
    • +

      MO23.04 - Is pre-trial quality assurance (QA) effective? A comparison of pre-trial QA versus ongoing QA for the CONVERT Trial. (ID 1809)

      10:50 - 10:55  |  Author(s): C. Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Background
      CONVERT is an international randomised phase III trial comparing 45Gy in 30 fractions twice-daily and 66Gy in 33 fractions once-daily (given concurrently with cisplatin/etoposide) for good performance status patients with limited stage small cell lung cancer. A QA programme was set-up to standardise radiotherapy (RT) delivery across all centres.

      Methods
      The pre-trial QA exercise (PQE) involved completion of a questionnaire and treatment planning exercise. Each participating clinician was asked to select a previously treated patient, who fitted the entry criteria for the trial, and provide disease and organs at risk (OAR) outlines and a treatment plan for both arms of the trial. QA guidelines, including an atlas for OAR outlining, were distributed to participating centres. Additionally, at least one RT plan per centre was randomly collected during the trial (ongoing QA exercise-OQE). A comparison was made between the PQE and OQE for each centre, including a review of eligibility criteria, OAR and gross tumour volume (GTV) outlining, expansion to clinical target volume (CTV) and planning target volume (PTV).

      Results
      Twenty nine clinicians from 28 centres who had completed both the pre-trial QA and the ongoing QA were included in the analysis. From the pre-trial questionnaire it was reported that 3 centres were using beam energies of 10MV or more which was not permitted as per protocol. Subsequently the PQE showed that these all used acceptable beam energies. Four clinicians submitted ineligible patients for the PQE and none for the OQE. Twenty five clinicians (86.2%) used the correct GTV to CTV and CTV to PTV expansions for the PQE and OQE. Table 1 shows a comparison of adherence to protocol regarding OAR outlining between the PQE and OQE. Table 1

      Oesophagus outline Spinal canal outline Heart outline Lung-PTV outline
      PQE-OAR outline as per protocol (n=29) 19 (65.5%) 14 (48.3%) 4 (13.8%) 20 (68.9%)
      OQE-OAR outline as per protocol (n=29) 21 (72.4%) 18 (62.1%) 8 (27.6%) 20 (68.9%)
      Organ at risk doses were found to be within the tolerances specified in the trial protocol for both PQE and OQE.

      Conclusion
      A PQE improves clinicians’ compliance to trial protocol, and has been found in the OQE to reduce deviations across the participating centres that may confound the results of the study. Despite the fact that consistency of OAR outlining remained an issue in both the PQE and the OQE an overall improvement was seen following the PQE.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

    • +

      MO23.05 - Changes in lung radiotherapy techniques during the CONVERT Trial. A survey of participating centres. (ID 1820)

      10:45 - 10:50  |  Author(s): C. Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Background
      CONVERT is an international randomised phase III trial, comparing 45Gy in 30 fractions twice-daily or 66Gy in 33 fractions once-daily (given concurrently with cisplatin/etoposide) for good performance status patients with limited stage small cell lung cancer. A survey was sent out to 69 clinicians who had randomised patients into the trial with the aim of establishing how radiotherapy techniques for lung cancer have changed over the 5 years since the trial opened.

      Methods
      As part of the pre-trial quality assurance process each centre was asked to complete a facility questionnaire giving details of treatment planning, delivery and verification techniques. Recruitment to the trial began in April 2008 and in January 2013, a further facility questionnaire was sent to centres. The survey was completed using an on-line survey tool.

      Results
      This analysis includes answers from the 34 clinicians who responded to the questionnaire. Changes in treatment planning techniques and verification since the beginning of the trial are summarised in table 1. Table 1 Figure 1 *Note that some centres reported using more than one beam arrangement, beam energy, planning algorithm or treatment verification technique. Out of the 34 clinicians who answered the questionnaire, 14 (41.1%) are currently using 4DCT, 3 (8.8%) are using breathold techniques and 16 (47.1%) are not using any technique to account for respiratory motion for simulation and treatment planning of lung patients. Data on management of respiratory motion were not available in 2008.

      Conclusion
      During the 5 years the CONVERT Trial has been open there have been significant advances in radiotherapy treatment technology. Major changes include the use of Type B treatment planning algorithms and PET CT for planning, IMRT for treatment and CBCT for treatment verification of patients with small cell lung cancer.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    MS20 - Small Cell Lung Cancer (ID 37)

    • Event: WCLC 2013
    • Type: Mini Symposia
    • Track: Medical Oncology
    • Presentations: 1
    • +

      MS20.3 - Optimal Radiotherapy for SCLC (ID 553)

      14:45 - 15:05  |  Author(s): C. Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Abstract
      Whilst the incidence of small cell lung cancer (SCLC) has reduced over the last 20 years, the prognosis of the disease remains poor. Major advances in SCLC include improvements in radiotherapy (RT) techniques, the use of prophylactic cranial irradiation (PCI) for all stages of SCLC and the improved integration of chemotherapy and RT. It is unlikely that future advances in the treatment of SCLC will relate to standard chemotherapy. The role of thoracic RT is well established in the management of stage I-III SCLC [1,2,3,4]. There is increasing evidence in the literature in favour of early concurrent chemo-radiotherapy (CTRT), and a gold standard of care for patients with a good performance status is twice-daily thoracic RT (45 Gy in 3 weeks) with concurrent cisplatin and etoposide [5]. Although current clinical trials are exploring the efficacy of new chemotherapeutic strategies, essential questions related to the optimisation of thoracic RT remain unanswered. These questions include i) optimal total dose, ii) fractionation, iii) timing and sequencing of radiation, iv) volume of irradiation, v) concurrent chemotherapy/targeted therapy combinations, and vi) the importance of the time between the start of any treatment to end of RT. PCI reduces the incidence of brain metastases and improves survival in all stages of SCLC [6,7]. As a result of the implementation of best standard of care the 5 year survival of stage I-III SCLC patients has increased from less than 10% with chemotherapy alone to 25-30% with early concurrent CTRT and PCI. It is crucial that patients with SCLC are given the opportunity to participate in clinical research in order to continue to improve the survival of this disease. Clinical trials aiming to establish a standard dose/fractionation in the stage I-III setting include the European/Canadian CONVERT and the US intergroup (CALGB 30610/RTOG 0538) studies. The results of the CREST study investigating the role of thoracic RT in stage IV SCLC are eagerly awaited. Molecular studies are ongoing aiming to gain improved insight into the molecular biology of SCLC, discover and/or validate candidate biomarkers for response, resistance to or toxicity of systemic treatment and radiation. There is now a concerted effort within the research community to understand the molecular mechanisms that underpin the molecular pathways in cancer. It is hoped that this understanding will lead to the development of targeted therapies that will not only prove efficacious, but also less toxic than more conventional treatments. In combination with newer techniques such as conformal RT and better imaging, it is hoped that the rates of long term survivors will increase significantly in the future. References 1 Bayman NA, et al. Radiotherapy for small-cell lung cancer-Where are we heading? Lung Cancer. 2009;63(3):307-14. 2 Sørensen M, et al. ESMO Guidelines Working Group. Small-cell lung cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up. Ann Oncol. 2010;21(Supplement 5):v120–v125. 3 Stahel R, et al. 1st ESMO Consensus Conference in lung cancer; Lugano 2010: small-cell lung cancer. Ann Oncol. 2011;22(9):1973-80. 4 Pignon JP, et al. A meta-analysis of thoracic radiotherapy for small-cell lung cancer. N Engl J Med 1992;327:1618-22. 5 Turrisi AT, et al. Twice daily compared to once-daily thoracic radiotherapy in limited-stage small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med 1999;340:265-71. 6 Auperin A, et al. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. Prophylactic Cranial Irradiation Overview Collaborative Group. N Engl J Med 1999;341(7):476-84. 7 Slotman B, et al. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007;357(7):664-72.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    O14 - Radiotherapy - Toxicity and Clinical Trials (ID 105)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Radiation Oncology + Radiotherapy
    • Presentations: 1
    • +

      O14.06 - Investigation of a Patient Reported Outcome (PRO) tool to assess radiotherapy-related toxicity in patients with lung cancer (ID 1614)

      11:25 - 11:35  |  Author(s): C. Faivre-Finn

      • Abstract
      • Presentation
      • Slides

      Background
      Discrepancies between clinician and patient reported symptoms validate the investigation of a PRO tool in clinical trials and routine practice. There is a paucity of data regarding the feasibility and relevance of PRO tools to assess radiotherapy toxicity in patients with lung cancer.

      Methods
      From January to June 2013, lung cancer patients undergoing thoracic radiotherapy or chemo-radiotherapy completed a PRO toxicity tool (adapted Radiogenomics Biorepository and Databank lung questionnaire) consisting of 9 patient-adapted Common Terminology Criteria for Adverse Events (CTCAE) items and World Health Organisation (WHO) performance status (PS) at baseline, at the end of radiotherapy and at 4-10 weeks follow-up (FU). At the same time points, patients completed the European Organisation for Research and Treatment of Cancer Quality of Life (QoL) Questionnaire along with its lung cancer specific module (EORTC QLQ-C30/LC13) and the Hospital Anxiety and Depression Scale (HADS). Clinicians completed the same CTCAE items for each time point. Agreement between patients’ and clinicians’ toxicity reports was assessed using weighted kappa coefficients. The patients’ QoL and HADS scores were correlated with the patients’ and clinicians’ reported toxicity using Spearman rank correlation coefficients.

      Results
      Of the 116 patients consented, 70 (85 paired responses) completed all 3 questionnaires for at least one time point excluding baseline. Median age was 71.5 years (39-89 years), 54.3% of the patients were male and 85.7% had a diagnosis of non-small cell lung cancer. Agreement between patients’ and clinicians’ reported toxicity ranged from poor to substantial (Figure 1). Perfect agreement was ≥50% for all assessed items with the exception of PS for both the end of radiotherapy and FU. The majority of discrepancies (≥74%) differed by 1 grade of toxicity. At the end of radiotherapy patients reported greater severity than clinicians for all items but not for PS; however this was less pronounced at FU. QoL scores were generally more strongly correlated with the patients’ compared to clinicians’ matching toxicity grades at the exception of dyspnoea. The correlation of HADS scores with patients’ CTCAE anxiety and depression grades ranged from moderate-to-low to moderate. There was no correlation with clinicians’ grading for depression and no-to-moderate correlation for anxiety. The adapted Radiogenomics Biorepository and Databank lung questionnaire demonstrated a high Cronbach’s α value (0.848) indicating good reliability. Figure 1

      Conclusion
      The use of a PRO tool in radiotherapy for lung cancer is feasible, reliable and acceptable to patients and complements the clinicians’ assessment. Further research is required to evaluate its validity.

      Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.

      Only Active Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login or select "Add to Cart" and proceed to checkout.

  • +

    P1.06 - Poster Session 1 - Prognostic and Predictive Biomarkers (ID 161)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Biology
    • Presentations: 1
    • +

      P1.06-053 - Clinical utility of circulating serum and plasma biomarkers for personalised radiotherapy treatment of non-small cell lung cancer (NSCLC) (ID 3098)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      Personalised strategies that tailor radiotherapy (RT) dose and schedule according to clinical and molecular factors, novel drug-RT combinations and/or advanced RT techniques are needed to optimise outcomes from RT for NSCLC. Development of such approaches would benefit from objective measures to inform on survival, chance of response and/or toxicity. We evaluated 26 circulating proteins and cytokines implicated in angiogenesis, metastasis, apoptosis, hypoxia and inflammation for prognostic (survival), predictive (RT response/toxicity) and/or pharmacodynamic significance in the context of RT for stage I-III NSCLC.

      Methods
      NSCLC patients donated blood prior to, serially and on completion of RT treatment. Samples were analysed for cell death (M30, M65, CYFRA), hypoxia (osteopontin, CA-IX), angiogenesis (Ang2, FGFb, HGF, VEGFA, VEGFC, PDGF, IL8, PlGF, KGF, VEGFR1, VEGFR2, Ang1, Tie2), metastatic (EGF, E-Selectin, VCAM1) and inflammatory (IL1b, IL10, IL12, TNFa, IL6) cytokines using single- or multi-plex ELISAs (SearchLight multiplex Aushon BioSystems, Peviva, R&D Systems). Clinical data were collected for age, gender, performance and smoking status, ace27 co-morbidity score, weight loss, TNM stage, haemoglobin, treatment received, various lung function and RT treatment parameters, histology, treatment received, toxicity, response and survival. Standard statistical methods were used to explore for associations and prognostic significance (Stata version 10).

      Results
      Seventy-eight patients were enrolled from March 2010 to August 2011: 61% male; majority (44%) squamous histology; 82% PS 0 or 1; 72% ex-smoker; 9% stage I/II, 44% stage IIIA, 47% IIIB; median age 66 years (range 31-86), 42% age > 70; 20% weight loss of 5-10%, 11% weight loss >10%; 62% prior chemotherapy/sequential RT, 20% concurrent chemoradiotherapy, 18% radiotherapy alone. RT treatment doses administered ranged from 50-55Gy in 20 fractions to 60-66 Gy in 33 fractions. Significant associations (p<0.05) were observed for EGF levels with gender and age, for FGFb with co-morbidity score and for IL8, IL1B and KGF with smoking status. Positive correlations of biomarkers at baseline (p<0.001) were observed for TNFa with FGFb, IL1b, IL8, IL12; FGFb with IL1b, IL8, IL12 KGF; IL1b with IL8, IL12; IL8 with KGF, IL12; KGF with IL12. In the overall population, at day 8 during RT significant decreases were observed for Ang2, EGF, E Selectin, FGFb, HGF, VCAM1, VEGFC & VEGFR2. Post completion of RT Ang2, EGF, E Selectin, FGFb, HGF & VEGFC levels remained significantly lower than at baseline prior to RT, and in addition significant global decreases in Ang1 and VEGFA were observed. The median survival overall was 16.8 months at a median follow up of 12 months. In univariate analysis there were non-significant trends to worse survival for older patients, weight loss >5%, higher TNM stage, higher co-morbidity scores and current smokers. Better survival was observed for patients with higher baseline levels of IL1b (p = 0.005) and TNFa (p = 0.022).

      Conclusion
      Preliminary analysis demonstrates appreciable changes of various circulating biomarkers during RT and identifies interleukin-1 beta and tumor necrosis factor alpha as potential prognostic factors. Multivariate analyses and correlation of biomarkers with response and toxicity are ongoing and will be presented.

  • +

    P1.09 - Poster Session 1 - Combined Modality (ID 212)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
    • +

      P1.09-011 - Phase I clinical trial assessing the MEK inhibitor selumetinib (AZD6244; ARRY-142886) with concomitant thoracic radiotherapy (RT) in patients with Stage III-IV non small cell lung cancer (NSCLC) (ID 1415)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      The RAS/RAF/MEK/ERK signalling cascade has a central role in cancer proliferation and in modulating response to treatment. RAS mutations can confer a radiation-refractory phenotype and MAPK signaling can be stimulated by treatment with ionizing radiation in non-small cell lung cancer (NSCLC). Selumetinib (AZD6244; ARRY-142886) is an orally available inhibitor of MEK1/2 which was shown to enhance the effect of radiotherapy in preclinical studies. This effect was due to the ability of selumetinib to directly sensitize tumor cells to the cytotoxic effect of radiation and to modulate tumor vessel functionality by reducing VEGF-A expression. In a Phase II study, selumetinib given in combination with docetaxel showed promising activity in NSCLC patients with KRAS activating mutations. Aim To determine the recommended Phase II dose (RP2D) of selumetinib in combination with standard dose thoracic radiotherapy (RT) in NSCLC.

      Methods
      Selumetinib (Hyd-Sulfate capsule) was administered orally twice daily as a single agent for one week and then in combination with thoracic RT for 6 to 6.5 weeks (60 to 66 Gy in 30 to 33 fractions) in a single institution, open label Phase I trial using a modified Fibonacci sequence. Prior standard chemotherapy was permitted with a minimum interval between day8 of the last cycle of chemotherapy and day1 of administration of selumetinib of ≥ 2weeks. Other eligibility included: histologic or cytologic diagnosis of NSCLC, stage III not suitable for concurrent chemo-radiotherapy or stage IV with dominant thoracic symptoms, disease encompassable within a radical RT treatment volume, ECOG PS 0-1., no prior RT or investigational agents.

      Results
      A total of six consecutive patients with inoperable stage III (n=3) or stage IV (n=3) NSCLC were given selumetinib 50 mg twice daily (dose level 1) with concomitant thoracic RT (59.8-66 Gy in 30-33 fractions). All patients completed the combined treatment. Selumetinib delivery was > 80%. Four out of the six patients had dose interruptions of 2-3 days due to expected adverse events (AEs). Skin rash (6/6), diarrhoea (5/6) and fatigue (4/6) were the most common toxicities. Grade 3/4 AEs included hypertension (2/6), diarrhoea (2/6), skin rash (1/6), pulmonary embolism (1/6), fatigue (1/6) and pericardial effusion (1/6). Pulmonary embolism (grade 3) was considered not related to the study treatment. One patient experienced dose limiting toxicity (DLT) consisting of a combination of diarrhoea (grade 3) and fatigue (grade 3). Response to treatment was assessed 4 weeks post RT. Distant recurrence was seen in 1 patient; 3 patients had SD, 1 patient experienced a PR and 1 a CR. Median duration of response was 2 months (range 1-4 months).

      Conclusion
      Selumetinib given at 50 mg twice daily with concomitant radical thoracic RT was tolerated with no unexpected toxicities or enhancement of expected RT toxicities. Although the protocol-defined criteria to further escalate the selumetinib dose were met, because of the heterogeneous and small patient cohort and AEs encountered further evaluation of the 50 mg twice daily was preferred in order to obtained additional safety data. An expanded cohort of 15 patients having additional FLT-PET scans.

  • +

    P2.09 - Poster Session 2 - Combined Modality (ID 213)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Combined Modality
    • Presentations: 1
    • +

      P2.09-008 - Concurrent chemoradiotherapy (cCTRT) for locally advanced Non Small Cell Lung Cancer (NSCLC) followed by consolidation Pemetrexed: a phase II study (ID 1545)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      cCTRT is the current standard treatment for good Performance Status (PS) unresectable locally advanced NSCLC. A phase III study demonstrated that Docetaxel consolidation does not improve overall survival (OS) after cCTRT (Hanna. JCO 2008). The role of consolidation chemotherapy after cCTRT is still investigational and our study was set up to evaluate the role of pemetrexed in this setting. A less toxic consolidation chemotherapy may enable a higher proportion of patients to comply to planned treatment which may improve outcome.

      Methods
      This was a single-institution prospective phase II study. Treatment comprised cisplatin (50 mg/m[2] days 1, 8, 29, 36), etoposide (50 mg/m[2] days 1-5 and 29-33) and concurrent thoracic radiotherapy starting on day 1 chemotherapy (66 Gy in 33 daily fractions; 3D conformal radiotherapy or IMRT) followed by consolidation pemetrexed (500 mg/m[2] on days 71, 92 and 133). The primary endpoint was 1 year OS. Secondary endpoints were progression-free survival (PFS), 2 yr OS, acute/late toxicity (CTCAE v3.0), compliance to treatment.

      Results
      35 patients were recruited between March 2008 and October 2010. Median age was 61 years (range 42-76). M:F ratio was 23(66%):12(34%). ECOG PS was 0:1 11(31%):24(69%). Histology: squamous 21(60%), adenocarcinoma 8(23%), undifferentiated 4(11%), other 2(6%). Stage: IIB 1(3%), IIIA 19(54%), IIIB 15(43%). All 35(100%) had PETCT staging. All 35 patients received concurrent chemotherapy (dose reduction in 3 patients) and 32 (91%) received the planned 66Gy (range 56-66 Gy). The number of patients who completed pemetrexed were: cycle 1=25 (71%), cycle 2=22 (63%), cycle 3=16 (46%). Radiation parameters: Gross Tumour Volume (GTV) was median 60.2 cm[3] (range 11.4-274.4 cm[3]), V~20Gy ~median 30.4% (range 10.5-35.3%), During the concurrent phase, grade 3/4 toxicity was noted for: neutropenia 17(49%) anaemia 1(3%), thrombocytopenia 1(3%), infection 8(23%), fatigue 6(17%), nausea±vomiting 4(11%), mucositis 3(9%), anorexia 3(9%). During the pemetrexed consolidation phase, the only grade 3/4 toxicities were: infection 5(20%), anaemia 3(12%), neutropenia 2(8%) and fatigue 2(8%). Acute radiotherapy toxicity (<3months): oesophagitis grade 3/4 10(29%) and late toxicity (>3months): pneumonitis grade 3/4 2(7%), oesophageal stricture 2 (7%), pulmonary fibrosis 1(3%). Median follow up was 25months. Median OS was 34months, with 1yr OS 77% (95% CI 60-88%), and 2yr OS 61% (95% CI 37-72%). Median PFS was 22months, with 1yr PFS 62% (95% CI 43-76%) and 2yr 49% (95% CI 31-65%). Of the 14 deaths, causes were, 1 suicide during radiotherapy, 2 treatment-related deaths (1 grade 5 pneumonitis and 1 grade 5 haemoptysis) and 13 due to lung cancer.

      Conclusion
      In an unselected locally advanced NSCLC population, staged with PETCT a median survival of 34 months can be achieved. The study reinforces the challenge of delivering consolidation chemotherapy and suggests that improved staging contributes to improved outcomes. Although there was failure to deliver all planned cycles of consolidation pemetrexed after cCTRT in 54% of patients, these are encouraging results that warrant further investigation.

  • +

    P2.24 - Poster Session 2 - Supportive Care (ID 157)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Supportive Care
    • Presentations: 1
    • +

      P2.24-034 - Treatment Beyond Progression in Patients with Non-Small Cell Lung Cancer Harbouring EGFR Mutations - The Manchester Lung Cancer Group Experience (ID 2431)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      The presence of EGFR activating mutations in NSCLC and sensitivity of these tumours to EGFR tyrosine kinase inhibitors (TKI) was first described in 2005. For NSCLC patients harbouring an activating EGFR mutation the treatment of choice is an EGFR TKI which is better tolerated and easier to administer than chemotherapy. However, questions remain about duration of therapy and optimal management on radiological progression.

      Methods
      A retrospective case note review was undertaken with the aim of establishing current practice in prescription and discontinuation of EGFR-TKIs, subsequent therapies and clinical outcomes. We identified consecutive patients from the database of the genetic testing laboratory (from Q4 2009 when routine testing commenced to a cut-off point of February 2013). 171 case- notes were reviewed for demographic and clinical data including survival.

      Results
      Of 171 cases 116 (69%) had received treatment with an EGFR TKI (Gefitinib 79%, Erlotinib 19%, both 2%). The reasons for not receiving treatment included: patient received radical therapy, patient died before oncology assessment and patient preference. 63% of patients were female, 26% never smokers, 44% ex-smokers, 6% current smokers and smoking history was not documented in 23%. 76% of patients had Stage IV disease and performance status was 0-1 in 47%, 2 in 22%, 3 in 7%, 4 in 2% and not documented in 23%. The average length of treatment on EGFR TKI was 10.5 months (range 0.5-40) and 36 (31%) patients were still on treatment at the time of analysis. Disease progression on the EGFR-TKI (PD) had occurred in 82 (71%) of patients and 28 (34%) of these continued EGFR TKI treatment beyond PD. The average length of time on treatment beyond PD was 5.6 months (range 1-16) and TKI treatment was ongoing in 9 of the 28 patients. 25 of the 73 patients (34%) with PD who had stopped EGFR TKI went onto receive a second line systemic treatment: pemetrexed and platinum 60%, gemcitabine and carboplatin 20%, single agent pemetrexed 8%, vinorelbine 8%, gemcitabine 4%. Third line therapy was received by 40% of those who had received 2[nd] line treatment.

      Conclusion
      Patients with EGFR activating mutations often derive a significant clinical benefit and marked reduction in tumour burden with oral EGFR TKI therapy, which results in a reluctance, from both patients and clinicians, to stop therapy at the time of radiological progression if the patient is still experiencing symptomatic improvement. Our results show that treatment beyond disease progression is common (34%) in ‘real –life’ clinical practice with some patients continuing to derive benefit for more than a year beyond the time of disease progression. .

  • +

    P3.11 - Poster Session 3 - NSCLC Novel Therapies (ID 211)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P3.11-024 - <strong>QUARTZ</strong><br /><strong>Quality of Life after Treatment for Brain Metastases from Non-Small Cell Lung Cancer: An update on the UK Medical Research Council QUARTZ trial.</strong> (ID 2154)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      Approximately one third of all non-small cell lung cancer (NSCLC) patients will develop brain metastases. The majority of such patients are inoperable with a very poor prognosis, and for several decades the standard treatment has been a combination of steroids and whole brain radiotherapy (WBRT). However, little evidence exists to support this approach, and there is continuing debate over the use of WBRT. The diversity of clinical opinion and patient preference makes this a challenging question to address.

      Methods
      The multi-centre randomised QUARTZ trial assesses whether optimal supportive care including steroids (OSC) is a viable alternative to the current standard of OSC plus WBRT, in terms of duration and quality of life (QoL). The primary endpoint of Quality Adjusted Life Years (QALYs) reflects that both quality and duration of survival are important. Disease status, symptoms and QoL data are collected weekly. The impact of the disease and treatment on carers is also being assessed. A total of 534 patients is required to exclude a detriment in terms of QALYs of >1 week with OSC (from 5 weeks with OCS plus WBRT), and the aim was to recruit this number in three years.

      Results
      After four years, only 188 patients had been recruited and a decision was taken to present the interim results to participating clinicians. Interim data (from the first 151 QUARTZ patients)[1] provided no strong evidence that omitting WBRT was detrimental in terms of survival or QoL and there were no clear differences in steroid usage or toxicity. By June 2013 QUARTZ has recruited 438 patients (82%) and 336 carers from 78 UK and Australian centres. Data collection is excellent with 98% of forms returned.

      Conclusion
      Patients with brain metastases (and others approaching end of life) represent a difficult group to study, as they often have different priorities regarding treatment options, but it is vital that we obtain the highest quality evidence possible in order to best guide treatment. QUARTZ has demonstrated that good trial design (weekly phone assessments, using QALYs as the primary endpoint, releasing interim results, etc) makes it possible to conduct successful clinical trials in this challenging patient population in order to answer important clinical questions. The interim results have reassured QUARTZ Investigators that omitting WBRT does not appear to lead to any detrimental effect in terms of either length or QoL, and have proved very useful when discussing the trial with potential patients. Although molecular targeted agents can extend treatment options for some patients, QUARTZ remains an important trial, which will define the use of WBRT and may impact on practice worldwide. We estimate completing recruitment during Summer 2014. Recruitment rates remain constant with many centres demonstrating successful recruitment to QUARTZ. Acknowledgements Thank you to all the patients and their carers for participating in the trial and the recruiting centres for their hard work in recruiting patients and helping to achieve the high standard of data collection. QUARTZ is supported by Cancer Research UK (CRUK/07/001). References 1. Langley RE et al. Clin Oncol (R Coll Radiol) 2013;25(3):e23-30.

  • +

    P3.13 - Poster Session 3 - SCLC (ID 202)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
    • +

      P3.13-005 - CONVERT - the challenges of opening centres and recruiting patients to an international multi-centre chemo-radiotherapy trial in limited-stage small cell lung cancer (ID 1366)

      09:30 - 09:30  |  Author(s): C. Faivre-Finn

      • Abstract

      Background
      CONVERT is a multicentre, randomised, phase III trial open in Europe and Canada in limited-stage small cell lung cancer. Patients are randomised to twice (45 Gy in 30 fractions) or once-daily radiotherapy (66 Gy in 33 fractions) given concurrently with 4-6 cycles of chemotherapy. This study is funded by Cancer Research UK and involves centres from the UK NCRI, the ‘Groupe Francais de Pneumo-Cancerologie’, the Spanish Lung Cancer Group, the EORTC and NCIC CTG.

      Methods
      To identify and review the challenges in site set-up. To review time taken from site initiation to first patient randomised, number of centres opened that included 0-2 patients and number of centres that recruited the majority of all patients.

      Results
      In June 2013, 519/532 patients had been recruited in 9 countries; 299 from 32 UK centres, 100 from 17 French centres, 39 from 9 Canadian centres, 27 from 6 Spanish centres, 26 from 3 Belgian centres, 13 patients from 1 centre in Slovenia, 9 from 2 centres in The Netherlands and 6 patients from 1 centre in Poland. Figure 1 shows the number of centres open and patients recruited. 96 sites are currently open to recruitment (5 sites opened in 2008, 34 in 2009, 31 in 2010, 17 in 2011, 8 in 2012 & 3 in 2013, 2 sites subsequently closed early) of which 74 (77%) have randomised at least 1 patient. 24 sites (25%) recruited only 1 or 2 patients. 10 sites have recruited 49% of the total number of patients with a single site recruiting 18.5% of all patients randomised. Time taken from site initiation to 1[st] patient randomised ranged from 0–1029 days with a median of 144 days. Time taken to complete the QA exercise from initial information sent to site ranged from 14-1181 days with a median of 290.5 days. Figure 1

      Conclusion
      Recruitment to an academic trial in LS-SCLC is a challenge but accrual has improved considerably since 2008. This can be directly related to the increasing number of sites opened to recruitment. Duration of site set-up and completion of the QA exercise are factors explaining slower than anticipated accrual rates particularly between 2008 and 2010. We anticipate that the study will close to recruitment in July 2013. International participation has been a key factor to the success of the trial and the experience gained will be of value to the design of future radiotherapy studies to ensure target accrual.