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Kai Wang
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JCSE01 - Joint IASLC-CSCO-CAALC Session (ID 63)
- Event: WCLC 2019
- Type: Joint IASLC-CSCO-CAALC Session
- Track:
- Presentations: 1
- Moderators:Chunxue Bai, Tony Mok, Yi-Long Wu, Qing Zhou, Nan Wu
- Coordinates: 9/07/2019, 07:00 - 11:15, Toronto (1985)
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JCSE01.14 - Higher Prevalence of EGFR Mutations Significantly Correlates with Lower PD-L1 Expression in Chinese Lung Adenocarcinoma (ID 3428)
07:00 - 11:15 | Author(s): Kai Wang
- Abstract
Abstract
Background
EGFR mutations are more prevalent in lung adenocarcinoma compared with other non-small cell lung cancer and are more prevalent in East Asians compared with the other populations. At the same time, we observed lower PD-L1 Tumor Proportion Score (TPS) in Chinese lung adenocarcinoma patients (pts) compared with that in Chinese lung squamous cell carcinoma pts and we also observed the proportion of PD-L1 positive (TPS >= 1%) in Chinese lung adenocarcinoma pts was lower than that in other multicenter cohorts. Then we hypothesize that the higher prevalence of EGFR mutations in Chinese lung adenocarcinoma pts correlates with lower PD-L1 expression.
Methods
The Origimed-based lung adenocarcinoma cohort was a retrospective cohort consisted of more than one thousand Chinese lung adenocarcinoma pts who underwent both NGS panel sequencing and PD-L1 immunohistochemistry (IHC) in a College of American Pathologists (CAP) certified and Clinical Laboratory Improvement Amendments (CLIA) certified laboratory during the year 2017 and 2018. Antibodies used in the PD-L1 IHC assay included 28-8 (sample size = 883) and 22C3 (sample size = 158). Tumor Proportion Score (TPS) was applied. All the slides were reviewed by the same senior pathologist. All the EGFR mutations were manually reviewed in Integrated Genomics Viewer for confirmation. After confirmation, each pts was assigned to EGFR positive group or EGFR negative group. Fisher' s exact test and Student' s t-test were applied.
Results
For antibody 28-8, PD-L1 IHC was positive (TPS >= 1%) in 18% (66/370) EGFR positive pts and was positive in 35% (180/513) EGFR negative pts (fisher exact test p value = 1.6e-5). For antibody 22C3, PD-L1 IHC was positive (TPS >= 1%) in 14% (9/64) EGFR positive pts and was positive in 45% (42/94) EGFR negative pts (fisher exact test p value = 3.8e-3). And we observed a significantly lower PD-L1 TPS in EGFR positive pts for both antibodies (t-test p value = 3.5e-11 for PD-L1 antibody 28-8; t-test p value = 6.0e-5 for PD-L1 antibody 22C3).
Conclusion
The observation demonstrated that lower PD-L1 TPS in Chinese Lung Adenocarcinoma pts was significantly correlated with East-Asian-specific high prevalence of EGFR mutations. The observation reassured that EGFR mutation status should be examined simultaneously with PD-L1 IHC in lung adenocarcinoma pts because it was a confounding factor for predicting immunotherapy outcome using PD-L1 TPS. The observation partly explained the generally higher PD-L1 TPS in Chinese lung squamous carcinoma pts compared with that in Chinese lung adenocarcinoma pts.
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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): Kai Wang
- 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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