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Yuankai Shi
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P47 - Small Cell Lung Cancer/NET - Biology / Translational (ID 234)
- Event: WCLC 2020
- Type: Posters
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P47.08 - Blood-Based Tumor Mutation Burden as a Predictive Biomarker for Clinical Benefit of Immunotherapy in Small-Cell Lung Cancer (ID 1697)
00:00 - 00:00 | Author(s): Yuankai Shi
- Abstract
Introduction
An exploratory analysis from the Checkmate-032 trial showed that the efficacy of nivolumab ± ipilimumab was enhanced in small-cell lung cancer (SCLC) patients (pts) with high tissue-based tumor mutational burden (tTMB). However, the availability of adequate tissue for genetic testing sometimes may be challenging. In this study, we aim to evaluate the reliability of blood-based TMB (bTMB) as a predictor for clinical benefit of immunotherapy in SCLC.
Methods
Pts with treatment-naïve, histologically or cytologically confirmed, limited- or extensive-stage SCLC were enrolled. Tumor tissue-derived DNA and plasma-derived ctDNA were obtained from these pts to perform a paired tumor-normal next-generation sequencing of 1021 cancer-related genes. TMB was determined as the number of somatic non-synonymous SNVs and Indels per Mb in the coding region (with variant allele fraction ≥0.03 for tTMB, and ≥0.005 for bTMB).
Results
Between Nov 2018 and Jan 2020, 30 pts with SCLC were enrolled. The median age at diagnosis was 61.5 years (range 43-69); 22 pts were male; 13 pts with extensive-stage SCLC, 16 pts with limited-stage SCLC, and one patient with unspecified pathology. Median tTMB was 9.6 muts/Mb (range 0-25.92), and median bTMB was 11.04 muts/Mb (range 0.96-21.12). No significant difference was observed in tTMB for pts with limited- and extensive-stage disease (median tTMB was 12.48 muts/Mb and 9.6 muts/Mb, respectively; p=0.3558). Pairwise comparison of tTMB and bTMB was shown in the Figure. A positive correlation between tTMB and bTMB was observed (Spearman rank correlation=0.7089, 95% confidence interval [CI]: 0.4594-0.8597, p<0.0001). TMB was categorized as high vs. low according to the upper quartile of two cohorts (cutoff: 14.4 muts/Mb for tTMB, and 13.33 muts/Mb for bTMB). The positive percentage agreement of bTMB was 87.5% (95% CI: 57.94%-117.06%), while the negative percentage agreement was 95.45% (95% CI: 86.00%-104.91%).
Conclusion
Our study suggested a strong correlation between bTMB and tTMB. Therefore, bTMB may be used as an attractive alternative to predict response to immunotherapy in pts with limited- or extensive-stage SCLC whose tumor tissue is not available.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 2
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.50 - Analysis of Efficacy and Safety of First Generation EGFR-TKI plus Apatinib in Treating Advanced NSCLC after EGFR-TKI Treatment Failure (ID 2642)
00:00 - 00:00 | Author(s): Yuankai Shi
- Abstract
Introduction
To investigate the efficacy, safety and survival of first generation epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) plus Apatinib in treating advanced lung adenocarcinoma with EGFR mutation after EGFR-TKI treatment failure.
Methods
This retrospective study comprised 31 patients with EGFR-sensitive mutated advanced lung adenocarcinoma who had progressed after first or second-line treatment of first generation EGFR-TKI. When the disease progressed, they received the original EGFR-TKI plus Apatinib until disease progression or unacceptable toxicity. The efficacy、safety and survival would be investigated. The Kaplan-Meier method was used to plot survival curve, and Log-rank test was applied for inter-group comparison. PFS1 was defined as the progression free survival of patients treated with single EGFR-TKI; PFS2 was defined as the progression free survival of patients treated with EGFR-TKI plus Apatinib.
Results
During monotherapy of EGFR-TKI, of the 31 patients, no one had complete response(CR), whereas 15 patients achieved partial response(PR),14 patients were with stable disease(SD),and 2 patients were with progressive disease(PD), representing an objective response rate(ORR) of 48.4%（15/31）,and a disease control rate (DCR) of 93.5%（28/31）.The median PFS1 was 10.6（95%CI：7.15~14.05）months. During the treatment of EGFR-TKI plus Apatinib, one patient did not undergo mid-term evaluation, of the remaining 30 patients, no one had CR, whereas 1 patient achieved PR, 26 patients were with SD, 2 patients were with PD, representing an ORR of 3.3%（1/30），and a DCR of 90%（27/30）. The median PFS2 was 6.6（95%CI：3.57-9.63）months. Log-rank test indicated that, EGFR-TKI as first-line treatment had a significant benefit of PFS1 than as second-line treatment (15.6 months VS 7.4 months, p = 0.02); EGFR-TKI plus Apatinib as second-line treatment had a significant benefit of PFS2 than as third-line treatment (7.6 months vs 3.0 months, p<0.001). The median PFS1 was significantly associated with the presence or absence of brain metastases prior to receiving EGFR-TKI monotherapy, patients without brain metastasis had better survival benefits (13.0 months vs 7.4 months, p=0.03). The median PFS2 was not significantly different from the presence or absence of brain metastases before treatment with EGFR-TKI plus Apatinib (7.6 months vs 4.4 months, p=0.19). Grade 4-5 adverse reactions did not occur during the treatment of EGFR-TKI plus Apatinib, 10 cases of grade 3 adverse reactions occurred, including 6 cases of hypertension, 2 cases of fatigue, and 1 case of diarrhea and hand-foot skin reactions respectively.
Conclusion
The first generation EGFR-TKI plus Apatinib is efficacious in treating patients with advanced lung adenocarcinoma with EGFR-sensitive mutations after EGFR-TKI treatment failure, PFS2 is extended and with acceptable toxic effects. Brain metastasis is one of the factors with poor prognosis in patients with advanced lung adenocarcinoma.
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P76.65 - CNS Efficacy of AST2818 in Patients with T790M-Positive Advanced NSCLC: Data from a Phase I-II Dose-Expansion Study (ID 3286)
00:00 - 00:00 | Presenting Author(s): Yuankai Shi
- Abstract
Introduction
Furmonertinib (AST2818, former name: alflutinib) is a new third-generation EGFR-tyrosine kinase inhibitor that selectively inhibits EGFR-sensitizing and EGFR T790M mutation. We have reported promising clinical activity and well-characterized tolerability of AST2818 in EGFR T790M-positive locally advanced or metastatic non-small-cell lung cancer (NSCLC) patients including its preliminary efficacy in patients with central nervous system (CNS) metastases (Shi Y et al JTO 2020;15(6):1015-1026). Herein, we report the result of recent subgroup analysis from phase I-II dose-expansion study (NCT03127449) where the CNS efficacy of different AST2818 doses was evaluated.
Methods
Patients aged ≥18 years with centrally confirmed EGFR T790M-positive locally advanced or metastatic NSCLC received AST2818 ranging from 40-240 mg doses once daily until disease progression. Patients with asymptomatic, stable CNS metastases not requiring steroids for at least 4 weeks before the first dose of AST2818 were enrolled. A subgroup analysis was conducted in patients with ≥1 measurable CNS lesion (per RECIST 1.1) at baseline brain imaging (CNS evaluable-for-response set, cEFR) and patients with ≥1 measurable and/or non-measurable CNS lesion at baseline brain imaging (CNS full analysis set, cFAS) by blinded independent central review (BICR). CNS efficacy was evaluated in terms of CNS objective response rate (ORR), CNS disease control rate (DCR), CNS progression-free survival (PFS), and CNS duration of response (DoR) (assessed by BICR).
Results
At data cutoff (29 January 2020), 116 patients were enrolled, of which 45 patients (38.8%) were included in cFAS and 23 patients (19.8%) were included in cEFR. Confirmed CNS ORR was 65.2% (15/23) while CNS DCR was 91.3% (21/23) in cEFR. The CNS ORR in the 40-, 80-, 160-, and 240-mg groups was 0 (no response of 1), 60% (3/5 partial response [PR]), 84.6% (1/13 complete response [CR] and 10/13 PR), and 25% (1/4 PR), respectively. In the cFAS, median CNS PFS was not reached (95% confidence interval [CI], 8.3 months to not reached), while median CNS PFS in 40-, 80-, 160-, and 240-mg groups were 2.8, 9.7, 19.3 months, and not reached, respectively. Median CNS DoR (19% maturity) in cFAS was not reached (range, 2.8 months to not reached). At 12 months, 50%, 81.8%, and 100% of patients were estimated to remain in response in 80-, 160-, and 240-mg groups, respectively.
Conclusion
AST2818 demonstrated clinically meaningful efficacy against CNS metastases. 160 mg provided relevant benefit with a high CNS ORR and PFS. Further studies are required to confirm these findings.
