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P. Allen



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    O02 - NSCLC - Combined Modality Therapy I (ID 111)

    • Event: WCLC 2013
    • Type: Oral Abstract Session
    • Track: Combined Modality
    • Presentations: 1
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      O02.03 - Value of Adding Erlotinib to Thoracic Radiation Therapy with Chemotherapy for Stage III Non-Small Cell Lung Cancer: A Prospective Phase II Study (ID 2436)

      10:30 - 12:00  |  Author(s): P. Allen

      • Abstract
      • Presentation
      • Slides

      Background
      The molecular basis for radiation resistance seems to involve an enhanced survival response with increased capacity for DNA repair and suppressed apoptosis. Both properties are controlled in part by upstream signal transduction pathways triggered by activation of the epidermal growth factor receptor (EGFR). Hypothesizing that the response of non-small cell lung cancer (NSCLC) to current standard chemoradiotherapy can be improved through the addition of therapy targeted to the epidermal growth factor receptor (EGFR), we undertook a single-institution phase II trial to test whether adding the EGFR tyrosine kinase inhibitor (TKI) erlotinib to concurrent chemoradiation therapy for previously untreated, locally advanced, inoperable NSCLC would improve survival and response rates without increasing toxicity.

      Methods
      Forty-eight patients with previously untreated NSCLC received radiation (63 Gy/35 fractions) on Monday‒Friday, with chemotherapy (paclitaxel 45 mg/m², carboplatin AUC=2) given every Monday and erlotinib (150 mg orally 1/d) Tuesday–Sunday for 7 weeks, followed by two cycles of consolidation paclitaxel-carboplatin. The primary endpoint was time to progression; secondary endpoints were toxicity; response, overall survival (OS), and disease control rates; and whether any endpoint differed by EGFR mutation status.

      Results
      Of 46 patients (96%) evaluable for response, 40 were former or never smokers; 23 had adenocarcinoma; and 41 were evaluable for EGFR mutations (37 wild-type [wt] and 4 mutations [all adenocarcinomas]). Median time to progression was 14.5 months and did not differ according to EGFR status. Toxicity was acceptable (no grade 5, one grade 4, and eleven grade 3). Fourteen patients (31%) had complete responses (3 mutations and 11 wt), 24 (52%) partial (20 wt and 4 unknown EGFR mutation status), and 8 (18%) had stable or progressive disease (6 wt, 1 mutation and 1 unknown EGFR mutation status); 3 patients with mutations (75%) had complete response vs. 11 wt (30%) (p=0.07 for EGFR mutation vs wt groups). For alive patients, the median follow-up was 44.7 months’ follow-up (range, 29.3–54.6 months). OS rates were 82.6% at 1 year, 67.4% at 2 years, 48.5% at 3 years, and 32.2% at 4 years and did not differ by mutation status (wt vs mutation, p=0.17). For all patients the median follow-up was 30.6 months’ follow-up (range, 3.4–54.6 months). 14 patients were free from progression and 32 had local failure, distant failure, or both. Eleven of the 27 distant failures were in the brain (7 wt, 3 mutation, 1 unknown; P=0.04); the local control rate was 75% among the 4 patients with EGFR mutations. Median time to progression was 13.6 months (95% confidence interval 10.2-20) and did not differ by EGFR status (wt vs mutation p=0.39).

      Conclusion
      Overall survival was promising, but time to progression was disappointing. Toxicity was acceptable. The prevalence of distant failures underscores the need for more effective systemic therapy, perhaps including maintenance EGFR-TKI for patients with mutated EGFR.

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    P1.11 - Poster Session 1 - NSCLC Novel Therapies (ID 208)

    • Event: WCLC 2013
    • Type: Poster Session
    • Track: Medical Oncology
    • Presentations: 1
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      P1.11-010 - Physical Targeting of Locally Advanced Non-Small Cell Lung Cancer (NSCLC): Proton Therapy (ID 1020)

      09:30 - 16:30  |  Author(s): P. Allen

      • Abstract

      Background
      Radiation therapy is a critical element in the potentially curative treatment of locally advanced NSCLC. Important developments have permitted more precise and effective physical targeting with radiations, an important complement to molecular targeting with drugs. Proton beam therapy (PBT) represents the most advanced physical targeting available thus far. A review of our experiences with proton therapy for NSCLC may serve as a benchmark for technically advanced radiation therapy.

      Methods
      Patients were enrolled on a protocol to investigate normal tissue effects of proton therapy between 2006 and December, 2010. Patients were excluded if they did not received concurrent chemotherapy, were treated on a phase II study of high dose PBT (JY Chang, PI) or were part of a randomized trial of PBT vs. intensity modulated radiation therapy (IMRT) (Z Liao, PI). They were evaluated before treatment with positron emission tomography (PET) and contrast enhanced computed tomography (CT), studies that were also used for planning treatment. Consultation with thoracic surgeons assured they were not candidates for resection. The mediastinal lymph nodes stations were evaluated with mediastinoscopy and/or fiberoptic bronchoscopy with ultrasound. Treatment planning consistently included motion management with 4D CT simulation and creation of an internal target volume (ITV). Patients were assessed for failure patterns and survival as well as normal tissue effects. Kaplan Meier estimates and Cox regression analysis were used to calculate survival outcomes.

      Results
      Of the 178 patients enrolled, the median age at diagnosis was 69 yrs (range 37.8 yrs to 94.9 yrs). KPS ranged from 60 to 100, median 80. 43% of patients had squamous carcinoma, and 57% had non-squamous histology. Stage distribution was 15% stage II, 65% III, 5% IV, 15% postoperative recurrence. The median tumor volume was 59 cc (range 4-753 cc) and the median total tumor dose was 74 Gy(RBE). Median follow-up time for living patients was 34.6 mos. Median survival was 32.7 mos. Three year survival rate was 46.5% (49.8% for squamous, 42.1% for non-squamous. Local failure at 3 years was 36.4% for squamous and 48.9% for non-squamous tumors. Distant metastasis-free survival at 3 years was 44.5% for squamous and 55.8% for non-squamous cell histology. Multivariate analysis found age, squamous histology and tumor size adversely affected survival.

      Conclusion
      Prognostic factors with PBT and concurrent chemotherapy are similar to those seen in series of patients treated with x-irradiation. Favorable median and 3 year survival rates with this relatively large data set suggest superior outcomes with PBT and quite possibly a new platform for physical targeting upon which to build chemical and molecular targeting strategies.