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Naoki Furuya
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P14 - Immuno-biology and Novel Immunotherapeutics (Phase I and Translational) - Immuno-Biology (ID 153)
- Event: WCLC 2020
- Type: Posters
- Track: Immuno-biology and Novel Immunotherapeutics (Phase I and Translational)
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P14.05 - The Relationship Between Genomic Alterations and the Efficacy of Immune Check Point Inhibitor for KRAS Mutated Non-Small Cell Lung Cancer (ID 1224)
00:00 - 00:00 | Presenting Author(s): Naoki Furuya
- Abstract
Introduction
KRAS mutation accounts for around 30% of oncogenic driver mutation in patients with advanced non-small cell lung cancer (NSCLC). Lower frequencies (around 10%) of KRAS mutation positive is seen in Asian subsets. The Check-Mate-057 trial revealed that nivolumab was more effective with KRAS mutation positive subset. However, there are some patients with no clinical benefit using immune check point inhibitors (ICIs) even with KRAS (+) / PD-L1 high expression patients. Recently, it has been suggested that co-occurrences of other genomic alterations (such as TP53, STK11 and LKB1) with KRAS might be a poor prognostic or predictive factor for ICIs. However, there are few reports that investigate the effects of genomic alterations and ICIs on KRAS mutant in Asian subsets
Methods
We prospectively analyzed NSCLC patients by next-generation sequencing (NGS, system, Oncomine™ Comprehensive Assay) in a nationwide genomic screening project (LC-SCRUM-Asia). The genomic database for LC-SCRUM-Asia was utilized for analysis.
Results
From July 2015 to February 2020, 190 patients were enrolled in LC-SCRUM-Japan at our hospital, 22 KRAS positive patients were identified (11.6%, G12A/G12C/G12D/G12V/G13D/Q61H: 3/7/3/6/2/1). All patients were histologically diagnosed with adenocarcinoma. The median age was 67 years (range, 53-84), and 16 (72.7%) were male. PD-L1 expression (22C3 antibody) was evaluated in 13 patients (high/low/none:10/2/1). Co-occurring genomic alterations were identified by NGS (TP53/STK11:14/2). Among 22 patients, 14 received anti-PD-1 inhibitor monotherapy after 1st line chemotherapy. Response rate of ICI monotherapy was 50.0% (7/14), and the disease control rate was 57.1% (8/14). Median overall survival (OS) was 26.8 months for ICI therapy (+) patients compared with 5.1 months for ICI therapy (-) patients (p<0.0001). In patients treated with ICI monotherapy, median OS was 26.8 months for TP53 (+) patients compared with 10.1 months for TP53 (-) patients (p=0.34).
Conclusion
KRAS mutated NSCLC patients demonstrated various clinical features depending on co-occurring genomic alterations. NGS analyses might be useful to predict or prognose ICI efficacy in KRAS mutated NSCLC patients.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.79 - Osimertinib in Poor PS Patients with T790M-Positive Advanced NSCLC after Progression of EGFR TKI Treatments (NEJ032B) (ID 3492)
00:00 - 00:00 | Author(s): Naoki Furuya
- Abstract
Introduction
Osimertinib has already been reported to be highly effective in epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) -resistant patients with T790M mutation-positive advanced non-small-cell lung cancer (NSCLC). However, its effectiveness and safety in those patients with poor performance status (PS) are unknown.
Methods
After progression by a treatment of gefitinib, elrotinib and/or afatinib patients who had T790M mutation, a Stage IIIB, IV or recurrence disease, and PS 2-4 were enrolled in this study. Osimertinib at a dose of 80 mg/day was orally administered. The primary endpoint of this phase II study was response rate (RR), and the secondary endpoints were progression free survival (PFS), overall survival (OS) and safety.
Results
Thirty-three patients were enrolled from February 2017 to May 2019. All patients met the eligibility criteria. Their median age was 72 years (range: 47–89). Women accounted for 81.8% of the patients, and 69.7% and 24.2% of the patients had a PS of 2 and 3, respectively. For 32 patients except for a patient with a protocol violation, the RR was 53.1% (95% confidence interval: 34.7-70.9%), and the disease control rate was 75.0%. The PFS was 4.8 months, and the OS was 11.1 months. Interstitial lung disease (ILD) at all grades and grade 3-5 were observed in 15.1% (5/33) and 6.1% (2/33), respectively, and treatment-related death by ILD occurred in one patient.
Conclusion
As the primary endpoint, we verified that osimertinib was sufficiently effective in EGFR TKI-resistant, poor PS patients with T790M mutation-positive advanced NSCLC. However, physicians should pay attention to relatively short PFS and adverse events such as ILD.
Clinical trial information: jRCTs061180018.
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P89 - Targeted Therapy - Clinically Focused - Translational (ID 266)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P89.06 - Prospective Concordance Study of a Multi-Gene PCR Assay and NGS for the Detection of Targetable Gene Alterations in Lung Cancer (ID 1688)
00:00 - 00:00 | Author(s): Naoki Furuya
- Abstract
Introduction
A rapidly increasing number of oncogenic drivers have been identified in non-small cell lung cancer (NSCLC) which has led to a shift towards next generation sequencing (NGS)-based testing as sequential single-gene testing is not feasible due to limited biopsy material and high frequency of depletion of samples. However, NGS testing is costly and the turnaround time is often longer than what is suitable for clinical decision making. The Amoy 9 in 1 test is a quantitative PCR (qPCR) assay covering 167 actionable variants across 9 genes of relevance in NSCLC. The test is in kit form that can be performed locally. The 9 in 1 test is being performed in parallel with the NGS test, Oncomine comprehensive assay 3.0 (OCA), in the international genomic screening project in East Asia (LC-SCRUM-Asia). We present the prospectively generated concordance data from the initial 1200 Japanese patients.
Methods
Fresh frozen tumor samples were collected from NSCLC patients of 206 institutions participating in the LC-SCRUM-Asia. DNA and RNA were extracted, and the 9 in 1 test and OCA were performed blinded to the results from the other assay in a central laboratory.
Results
Of the 1200 patients enrolled since June 2019 to February 2020, 801 were men, 399 women, 90% had adenocarcinoma, 10% other NSCLC. Success rate for the 9 in 1 test: 99%, for OCA: 93%. Median turnaround time for the 9 in 1 test: 3 days, for OCA: 21 days. The frequencies of genetic alterations detected by the 9 in 1 test were 309 EGFR (26%) of which 24 ex20ins (2%), 145 KRAS (12%) of which G12C 40 (5%), 42 ALK fusions (4%), 35 MET ex14skip (3%), 21 RET fusions (2%), 18 HER2 ex20ins (2%), 17 BRAF V600E (1%) and 13 ROS1 fusions (1%). Overall percent agreement (%), positive percent agreement (%) and negative percent agreement (%) of the 9-1 test compared with OCA for alterations in EGFR (98, 96 and 99), EGFR exon 20 insertions (99, 100 and 99), KRAS (98, 95 and 98), KRAS G12C (99, 100 and 99), ALK (99, 91 and 99), MET exon 14 skip (99, 96 and 99), RET (99, 94 and 99), HER2 (99, 100 and 99), BRAF V600E (100, 100 and 100), and ROS1 (99, 100 and 99).
Conclusion
The results of 9 in 1 multi-gene qPCR assay were highly concordant with those of the NGS assay for alterations (fusions, ins/dels, SNVs) in all 9 genes included in the assay with an overall percent agreement for alterations by each gene of 98% or higher. With a high success rate (99%) and a short turnaround time (3 days), the assay has advantages compared to NGS as a tool to enable precision medicine in 1st-line advanced NSCLC patients.
