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Chao-Hua Chiu



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    EP1.14 - Targeted Therapy (ID 204)

    • Event: WCLC 2019
    • Type: E-Poster Viewing in the Exhibit Hall
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
    • Moderators:
    • Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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      EP1.14-35 - Squamous Cell Carcinoma Transformation After Acquired Resistance to Osimertinib  (Now Available) (ID 85)

      08:00 - 18:00  |  Author(s): Chao-Hua Chiu

      • Abstract
      • Slides

      Background

      Osimertinib is a third-generation epidermal growth factor receptor - tyrosine kinase inhibitor (EGFR-TKI) for the management of NSCLC carrying EGFR T790M mutation after acquired resistance to prior EGFR-TKI and is now the preferred therapy in the front-line. The resistance mechanism of osimertinib, including histologic transformation had been reported, mostly small cell carcinoma.

      Method

      Here we a patient with lung adenocarcinoma with uncommon EGFR H835L +L833V + T790M mutation who developed progressive lung atelectasis after acquired resistance to osimertinib. Bronchoscopic biopsy over the endobronchial tumor was done and the pathology report showed squamous cell carcinoma.

      Result

      Mutation analysis of the squamous cell carcinoma performed by next generation sequencing (FoundationOne® CDx) was performed and reveled complex genomic alteration including EGFR H835L, L833V and T790M mutation, TP53 mutation and mTOR amplification. Squamous cell transformation after acquired resistance to osimeritinib was diagnosed. Then the patient was treated with a mTOR inhibitor, everolimus (5mg /day) plus osimertinib. One month after treatment an initial tumor response was observed, however, a progression occurred after 3 months of treatment.

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      Conclusion

      Squamous cell transformation is a rare manifestation of osimertinib resistance, further research is need to investigate the underlying mechanism of this histologic change and discover the proper treatment strategy.

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    OA02 - A New Vision of Targets and Strategies (ID 120)

    • Event: WCLC 2019
    • Type: Oral Session
    • Track: Targeted Therapy
    • Presentations: 1
    • Now Available
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      OA02.03 - The Third Generation EGFR Inhibitor (EGFR-TKI) HS-10296 in Advanced NSCLC Patients with Resistance to First Generation EGFR-TKI (Now Available) (ID 766)

      10:30 - 12:00  |  Author(s): Chao-Hua Chiu

      • Abstract
      • Presentation
      • Slides

      Background

      HS-10296 is an oral, potent, high selective third generation EGFR tyrosine-kinase inhibitor (EGFR-TKI) for sensitizing mutations, and the EGFR Thr790Met (T790M) resistance mutation which has been demonstrated by phase I study. This phase II, open-label, multicenter single-arm study was designed to confirm the efficacy and safety of HS-10296 in a large population of non-small-cell lung cancer (NSCLC) patients with EGFR T790M mutation, who had progressed after first generation EGFR-TKI treatment.

      Method

      Patients aged at least 18 years with centrally confirmed EGFR T790M-positive mutations, locally advanced or metastatic (stage IIIB/IV) NSCLC after first generation EGFR-TKI treatment received HS-10296 110 mg orally once daily until disease progression, or intolerable toxicity, or patient withdrawal. Patients with asymptomatic, stable brain metastases not requiring steroids were allowed to enroll. The primary endpoint was the objective response rate (ORR) by independent central review using Response Evaluation Criteria in Solid Tumors, version 1.1 every 6 weeks. Response endpoints (ORR and disease control rate [DCR]) were assessed in response analysis set. Secondary end points including progression-free survival (PFS), duration of response (DoR), depth of response (DepOR), overall survival (OS) and safety were evaluated in full analysis set. The final data cutoff was on Jan 5, 2019. The study is still ongoing.

      Result

      Totally, 244 patients (median age 60.8) entered study in 36 sites in mainland China (189 patients) and Taiwan (55 patients) between May 16, 2018 to Oct 23, 2018. 2 patients were excluded from the evaluable for response analysis set (n=242) due to absence of measurable disease at baseline by independent central review. At data cutoff, 182 (74.6%) patients remained on treatment. The median duration of follow-up was 4.7 months. 160 of 242 patients achieved confirmed partial responses by independent central review. The ORR was 66.1% (95% CI: 59.8-72.1). The DCR was 93.4% (95% CI: 89.5-96.2). The most common adverse reactions (≥ 10%) were blood creatine phosphokinase increased (43 [17.6%]), aspartate aminotransferase increased (29 [11.9%]), pruritus (28 [11.5%]), rash (28 [11.5%]) and alanine aminotransferase increased (26 [10.7%]). The most common all-causality grade 3 and 4 adverse events were blood creatine phosphokinase increased (14 [5.7%]) and hyponatraemia (4 [1.6%]). Serious adverse events were reported in 30 (12.3%) patients, of which 19 (7.8%) were investigator assessed as possibly treatment-related to HS-10296. Three deaths were due to adverse events; one was related to cardiopulmonary failure, other two events occurred after disease progression. There was no interstitial lung disease during study treatment.

      Conclusion

      HS-10296 has demonstrated good clinical benefit with minimal toxicity in patients with EGFR T790M-positive NSCLC patients who have progressed after first generation EGFR-TKI treatment. The Phase III study has already launched comparing HS-10296 with gefinitib in advanced NSCLC patients with EGFR sensitizing mutations. (The study was sponsored by Jiangsu Hansoh Pharmaceutical Co., Ltd.; ClinicalTrials.gov number, NCT02981108)

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    P1.17 - Treatment of Early Stage/Localized Disease (ID 188)

    • Event: WCLC 2019
    • Type: Poster Viewing in the Exhibit Hall
    • Track: Treatment of Early Stage/Localized Disease
    • Presentations: 1
    • Moderators:
    • Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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      P1.17-16 - Neo-Adjuvant Targeted Therapy in Non-Small Cell Lung Cancer Patients: A 10-Year Experience in a Tertiary Medical Center (ID 1018)

      09:45 - 18:00  |  Author(s): Chao-Hua Chiu

      • Abstract
      • Slides

      Background

      Epidermal growth factor receptor (EGFR) Tyrosine kinase inhibitor (TKI) or anaplastic lymphoma kinase (ALK) inhibitor had can provide dramatic response in lung adenocarcinoma patients, and have been the first line treatment for stage IV patients with corresponding genes mutations. Recent clinical trials had demonstrated both safety and tolerability in neo-adjuvant settings. However, there are still limited clinical data regarding long-term outcome and additional adjuvant treatment options. Our purpose was to investigate the treatment response and image change of neoadjuvant target therapy in non-small cell lung (NSCLC) cancer patient patients.

      Method

      Taipei Veterans General Hospital Lung Cancer Database was used to search for stage I to stage III NSCL patients, who’s first line treatment was TKI. Their medical records and chest CT and PET images were reviewed.

      Result

      We identified 20 patients in a 10 year period (January 2007 - December 2017) receive neoadjuvant TKI. 2 failed to receive further surgery treatment. One of them was due to disease progression while the other remained non-operable despite tumor sized down. The overall response rate for neoadjuvant TKI was 86%. 17 patients were clinical stage IIIA(AJCC 8th edition), 1 was IIIB, 2B and 1b. One of them received ALK inhibitor while the others received EGFR TKI. The mean duration of neo-adjuvant therapy was 73 days. For 18 patients receiving surgical treatment, 12 experienced down-staging (one got pathological complete response). 13 patients received adjuvant therapy with great variety. 7 patients did not have recurrent disease after surgery, and they all had pathological down staging. The median recurrence-free survival and overall survival was 13.7 months and 6 years, respectively.

      Conclusion

      As long-term survival was potentially achievable in such patient group, and with the diverse treatment options, results from randomized clinical trials are needed to give solid conclusion.

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