Virtual Library

Start Your Search

Jonathan Hicks



Author of

  • +

    P1.13 - Targeted Therapy (Not CME Accredited Session) (ID 945)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.13-17 - Multicentre Phase II Trial of First-Line Afatinib in Patients with Suspected/Confirmed EGFR Mutant NSCLC: ctDNA & Long-Term Efficacy (ID 11908)

      16:45 - 18:00  |  Author(s): Jonathan Hicks

      • Abstract
      • Slides

      Background

      Efficacy of afatinib in EGFR mutant patients with comorbidities or those with suspected EGFR mutations unfit for chemotherapy is poorly explored. We evaluated afatinib in this population, with serial plasma ctDNA to investigate the role of molecular EGFR genotyping and monitoring.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Phase-II trial enrolled NSCLC patients with comorbidities precluding chemotherapy, and either (i) EGFR-mutation, PS 0-3, or (ii) suspected EGFR-mutation (tissue unavailable/failed genotyping), never/former-light smoker, adenocarcinoma, and PS 0-2. Afatinib (40mg daily) given until progression/toxicity. Blood samples obtained at baseline and 12-weekly until discontinuation; plasma ctDNA performed using InVisionSeq™ (amplicon-based NGS).

      4c3880bb027f159e801041b1021e88e8 Result

      39 patients recruited (14 UK centres). Median age 72 years; 27 PS 0-1/12 PS 2-3. 21 patients (54%) had known tissue EGFR-mutations. Additional 8 patients with unknown tissue status (8/17;47%), were ctDNA EGFR-mutant, making 74% EGFR-mutant in total (29/39). Combined tissue and ctDNA data identified 21 patients with common mutations (exon 19/L858R), 8 with rare mutations (exon 18/20), and 10 suspected only. Corresponding median PFS of these cohorts were 10.2/3.9/5.3 months, with 6-month PFS of 71/38/50% all exceeding the 30% target; median OS were 24.8/5.7/11.4 months (p<0.001). Therefore, all patient groups benefitted; known EGFR-mutants having best outcomes. In April 2018, 5/39 patients survived >36 months, including 4/39 progression-free (median follow-up 33 months, maximum 55). Patients with ctDNA mutation clearance during afatinib treatment had substantially improved outcomes compared to those without clearance (Figure). 40% (4/10) of mutant cases who discontinued after 3 cycles because of progressive disease developed an exon 20 EGFR-mutation.

      timelyresults2.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      Patients unsuitable for chemotherapy with confirmed/suspected EGFR-mutations by tissue or ctDNA benefit from afatinib. Serial ctDNA is a potentially useful stratification and monitoring tool; amplicon-based ctDNA analysis can identify EGFR mutations when tissue is unavailable. Exon 20 mutations were observed at acquired resistance. ctDNA clearance during afatinib treatment is strongly associated with better PFS/OS.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.

  • +

    P1.16 - Treatment of Early Stage/Localized Disease (Not CME Accredited Session) (ID 948)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/24/2018, 16:45 - 18:00, Exhibit Hall
    • +

      P1.16-26 - Safety of SABR (Stereotactic Ablative Body Radiotherapy) for Central Non-Small Cell Lung Cancers (cNSCLC) with 50 Gray in 5 Fractions (50Gy/5f) (ID 12732)

      16:45 - 18:00  |  Author(s): Jonathan Hicks

      • Abstract
      • Slides

      Background

      SABR using 60Gy/3f (or equivalent) caused high toxicity when used for cNSCLC. To determine a safe SABR dose for cNSCLC, the phase I/II RTOG 0813 trial used 50Gy/5f as a baseline. From 2013, 50Gy/5f was adopted for inoperable early-stage cNSCLC at the West of Scotland Cancer Centre, a tertiary-level oncology unit. We report our prospectively collected toxicity and efficacy data.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with cNSCLC were identified from the radiotherapy database. cNSCLC was defined as lung cancers within 2cm of the proximal bronchial tree, or the planning target volume (PTV) abutting the mediastinal pleura/pericardium. Patient and treatment characteristics were obtained from electronic medical records. All patients received 50Gy/5f on alternate days with a volumetric arc therapy plan using TrueBeam linear accelerators. Toxicity was assessed in a centralised follow-up clinic 2 weeks, 6 weeks, 3 months, 6 months, 1 and 2 years after treatment using Common Toxicity Criteria Adverse Events version 3. Patients had a CT scan at 3 months post-treatment. Subsequent CT scans were at the discretion of the treating clinician.

      4c3880bb027f159e801041b1021e88e8 Result

      50 patients (31 females, 19 males, median age 75.1 years old) were identified with T1-2N0M0 cNSCLC. 84% were medically unfit for surgery. 40% had biopsy-proven NSCLC. All patients completed treatment on schedule. Two patients died within 90 days of treatment, one from a chest infection, the other cause of death was unknown. Table 1 describes the early and late toxicity. Over a median follow-up of 24 months, there were 20 deaths, 8 unrelated to cancer, and 12 due to cancer recurrence. The median progression free survival and overall survival are 26.0 months (95% confidence interval: 16.4, 35.6 months) and 28.6 months (95% confidence interval: 21.3, 35.8 months) respectively.

      world lung abstract table 1.jpg

      8eea62084ca7e541d918e823422bd82e Conclusion

      This study has demonstrated that 50Gy/5f is a safe dose and fractionation for early-stage inoperable cNSCLC, with outcomes comparable to other series.

      6f8b794f3246b0c1e1780bb4d4d5dc53

      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.