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Gee-Chen Chang
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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
- Moderators:Frank Griesinger, Luis Paz-Ares
- Coordinates: 9/08/2019, 10:30 - 12:00, Seoul (2007)
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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): Gee-Chen Chang
- Abstract
- Presentation
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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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-59 - Osimertinib in EGFR T790M Advanced NSCLC: Analysis of Uncommon/Complex EGFR Mutations in a Real-World Study (ASTRIS) (ID 1263)
10:15 - 18:15 | Author(s): Gee-Chen Chang
- Abstract
Background
The challenges of treating uncommon/complex EGFR mutations impact treatment decisions in clinical practice. Osimertinib is a third-generation, irreversible, oral EGFR-TKI that potently and selectively inhibits both EGFR-TKI sensitising (EGFRm) and EGFR T790M mutations and has demonstrated efficacy in NSCLC CNS metastases. ASTRIS is an ongoing, international, real-world study of osimertinib in EGFR T790M positive advanced NSCLC (NCT02474355). We report a subset-analysis of patients with uncommon/complex mutations.
Method
Patients with stage IIIB/IV T790M positive NSCLC previously treated with an EGFR-TKI were enrolled and received osimertinib 80 mg once-daily. Progression-free survival (PFS), clinical response and time to treatment discontinuation (TTD) were analysed in both full analysis set (FAS) and patients with uncommon/complex EGFR mutations. Uncommon mutation combinations included: T790M+G719X, T790M+S768I, T790M+ex20ins; complex mutations included T790M+two or more mutation(s).
Result
From 18 September 2015 to 15 October 2018 data cut-off, 3015 patients across 16 countries had received ≥1 dose of osimertinib (FAS), 53(2%) of these patients had uncommon/complex EGFR mutations. Baseline demographics between this patient subset and the FAS were similar (Asian: 55%/69%; female: 57%/64%; median age: 59 [30–80] years/62 [range, 27–92]; WHO performance status 2: 9%/11%, respectively). Baseline EGFR mutation status at enrolment of the FAS is shown in Table 1. Clinical outcomes appeared to be lower in the uncommon/complex mutation subset than in the FAS: response rate (measured in a FAS subset with ≥1 documented response assessment) was 50% [95% CI, 35.2, 64.8] in the uncommon/complex mutation group, and 57% [55.2, 58.9] in the FAS; median PFS was 8.1 [5.4, 10.1] and 11.1 [11.0, 12.0] months; median TTD was 9.0 [6.7, 11.5] and 13.5 [12.6, 13.9] months, respectively. Overall survival data are immature.
Conclusion
Whilst clinical outcomes appeared to be lower in the uncommon/complex mutation subset than the FAS, they were favourable and support use of osimertinib 80mg in this heterogeneous population.
