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Gregory A. Otterson



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    OA12 - Novel Therapies in MET, RET and BRAF (ID 921)

    • Event: WCLC 2018
    • Type: Oral Abstract Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/25/2018, 15:15 - 16:45, Room 106
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      OA12.02 - Updated Antitumor Activity of Crizotinib in Patients with MET Exon 14-Altered Advanced Non-Small Cell Lung Cancer (ID 13453)

      15:25 - 15:35  |  Author(s): Gregory A. Otterson

      • Abstract
      • Presentation
      • Slides

      Background

      MET exon 14 alterations occur in ~3% of non-squamous non-small cell lung cancer (NSCLCs) and 20–30% of sarcomatoid lung carcinomas. Here we present updated antitumor activity for crizotinib in patients with advanced NSCLC whose tumors are positive for MET exon 14 alterations (hereafter MET exon 14-positive NSCLC), including updated biomarker analyses in circulating tumor DNA (ctDNA).

      a9ded1e5ce5d75814730bb4caaf49419 Method

      Patients with MET exon 14-positive NSCLC by local molecular profiling were treated with 250 mg crizotinib BID in an expansion cohort of the ongoing PROFILE 1001 study (NCT00585195). Responses were based on derived investigator assessment per RECIST v1.0. Prospective plasma profiling for MET exon 14 alterations in plasma ctDNA was performed (PlasmaSELECT-R64; Personal Genome Diagnostics, Boston, MA).

      4c3880bb027f159e801041b1021e88e8 Result

      As of Jan 31, 2018, 69 patients (65 response-evaluable) with MET exon 14-positive NSCLC had been treated. Median age was 72 y (range: 34, 91). Tumor histology was: 84% adenocarcinoma, 9% sarcomatoid adenocarcinoma, 4% squamous cell carcinoma and 3% adenosquamous carcinoma. 61% were former-smokers, 38% never-smokers and 1% a current smoker. Median duration of treatment was 7.4 mo (95% CI: 5.5, 9.1), with 29% of patients ongoing. Confirmed responses were 3 CRs and 18 PRs (ORR, 32% [95% CI: 21, 45]); 29 patients had SD as their best overall response (Figure).

      crizo cmet ex14 waterfall_4may2018-v3.jpg

      Median time to response was 7.6 weeks (range: 3.7, 16.3). Median DOR was 9.1 mo (95% CI: 6.4, 12.7). Median PFS was 7.3 mo (95% CI: 5.4, 9.1). MET exon 14 alterations were detected in ctDNA from 18/37 (49%) patients with analyzable samples.

      8eea62084ca7e541d918e823422bd82e Conclusion

      In patients with MET exon 14-positive advanced NSCLC, crizotinib treatment led to objective responses that were rapid and durable, with CRs in some cases. Plasma ctDNA profiling detected MET exon 14 alterations in a subset of patients who harbor MET exon 14 alterations by tumor testing.

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    P3.17 - Treatment of Locoregional Disease - NSCLC (Not CME Accredited Session) (ID 983)

    • Event: WCLC 2018
    • Type: Poster Viewing in the Exhibit Hall
    • Track:
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/26/2018, 12:00 - 13:30, Exhibit Hall
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      P3.17-20 - Impact of Significant Primary Tumor Size Reduction on Radiation Dose to Normal Structures in Patients Receiving Definitive Chemoradiotherapy (ID 14327)

      12:00 - 13:30  |  Author(s): Gregory A. Otterson

      • Abstract

      Background

      Kilo-voltage cone beam computed tomography (kV-CBCT) allows for tumor localization and response assessment during definitive chemoradiotherapy (CRT) for locally advanced non-small cell lung cancer (LA-NSCLC). Previously we have analyzed patients with LA-NSCLC treated with definitive CRT accompanied with daily CBCT in our department and found that significant primary tumor volume loss occurs relatively early during treatment; and that greater tumor volume loss during treatment correlates with improved disease control and overall survival. It is not a standard practice to re-simulate patients for smaller target volume; but decreased tumor volume and consequent increase in air density could lead to increased radiation dose to the surrounding normal tissue such as the spinal cord. We hypothesize that increased air density secondary to tumor size reduction leads to increased dose to normal tissue including spinal cord, heart, esophagus and normal lung.

      a9ded1e5ce5d75814730bb4caaf49419 Method

      kV-CBCT images were imported to Eclipse treatment planning system. Primary tumors were re-contoured, and all normal tissue structures were readjusted based on the new images. Doses to the spinal cord, esophagus, normal lung, original planning target volume (PTV) as well as the new, smaller, PTV were re-calculated based on the original prescription dose and compared with the original plan by paired student t-test. The Acuros XB advanced dose calculation algorithm was used for all patients.

      4c3880bb027f159e801041b1021e88e8 Result

      Nine patients with greater than 40% target volume reduction after 4 weeks of CRT were analyzed. There is a mean size reduction of 425.1 cc (55.6%) in PTV (p=0.002). Mean dose to the new PTV is 50 cGy (0.8%) less than the prescription dose (average 6088 cGy) (p=0.07). 0.03 cc of PTV receiving the highest dose is 110 cGy (1.8%) less than originally planned. There is no significant dose difference to the normal tissue, including esophagus (D0.03cc, DMean, V105%, V50 Gy and V60 Gy), heart (D0.03cc, DMean, V30Gy and V45Gy), ipsilateral lung (DMean, V5Gy, V10 Gy, V20 Gy, V30 Gy) and total lung (DMean, V5Gy, V10 Gy, V20 Gy, V30 Gy).

      8eea62084ca7e541d918e823422bd82e Conclusion

      Despite significant primary tumor size reduction, there is no clinically significant difference in dose delivered to the primary tumor or to the radiation sensitive critical organs. Therefore the orinigal treatment plan can be safely used.

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