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Yasushi Goto
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MS 12 - Sustainable Care System in Each Region (ID 534)
- Event: WCLC 2017
- Type: Mini Symposium
- Track: Regional Aspects/Health Policy/Public Health
- Presentations: 5
- Moderators:Yasushi Goto, M.E. Hand
- Coordinates: 10/17/2017, 11:00 - 12:30, Room 501
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MS 12.01 - Sustainable Care System in North America (ID 7698)
11:00 - 11:15 | Presenting Author(s): Glenwood Goss, Natasha B Leighl
- Abstract
- Presentation
Abstract not provided
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MS 12.02 - Sustainable Care System in Europe (ID 8122)
11:15 - 11:30 | Presenting Author(s): Solange Peters
- Abstract
Abstract not provided
Information from this presentation has been removed upon request of the author.
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MS 12.03 - Sustainable Care System in China (ID 7869)
11:30 - 11:45 | Presenting Author(s): Yi-Long Wu
- Abstract
- Presentation
Abstract not provided
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MS 12.04 - Sustainable Care System in Philippines (ID 7699)
11:45 - 12:00 | Presenting Author(s): Gerardo de Hitta Cornelio
- Abstract
- Presentation
Abstract:
The Philippines is an archipelago composed of more than 7000 islands and is considered one of the emerging economies in Asia. Hence, it is not a surprise that although there is a huge improvement seen in the country, providing sustainable healthcare, even though it is in the list of the government’s priorities, is still a major problem. Cancer, as reported by the Philippine’s Department of Health (DOH) is the third leading cause of mortality behind Infectious and Cardiovascular Diseases. The top malignancy cases reported by the DOH involve the Breast, Lung, Prostate, Cervical and Colorectal. Incidence rates are highest in more developed countries due to early detection of the disease therefore in areas like the Philippines, which lacks access to early diagnosis and treatment, mortality rates remain high. One reason surmised besides lack of financial back up is the geography of the country. With more than 7107 and rising islands, health care delivery is more challenging due to most towns, especially in the southern parts of the country, are difficult to go to or inaccessible by land, air and/or sea. However, in spite of lack thereof, the Department of Health – Philippine Cancer Control Program established in 1990, with Administrative Order 89-A, continue to work hard to bridge the gap. Its mission is to reduce cancer morbidity and mortality in the country operating in a systematic and organized approach utilizing primary and secondary prevention at the community level and tertiary prevention in the different regions of the country through hospitals and community levels. By means of the 6 pillars namely, Epidemiology & Research; Public Information & Health Education; Prevention & Early Detection; Treatment; Training; and Pain Relief (focusing on subprograms involving breast, lung and cervical cancer control, cancer pain relief), a healthcare system that is sustainable was hoped to be established. There are numerous projects formulated using the 6 pillars however due to lack of financial support, stricter implementations of guidelines and slow government approvals into law, mortality from cancer continues to rise. Nonetheless, the program as well as medical societies such as the Philippine Society of Medical Oncology, Philippine Cancer Society, Philippine Society of Oncology, Philippine College of Surgeons and so on, remain confident and continue to work towards the goal. Programs, such as the Philippine Medicines Policy of 2011 employed strategies that would provide free medicines in the hope to address priority diseases such as TB, HIV, Malaria and Cancer. The Philippine Health Insurance Corporation in 2012 provided Benefit Packages in the aim of giving assistance to marginalized sectors of society afflicted with certain malignancies and promote patient empowerment to become active participants in healthcare decision-making by being informed and educated about their illness and adhering to treatment plans. Republic Act 10606 (The Universal Health Care Act of 2013), ensures that all Filipinos, especially the poorest of the poor, will receive health insurance coverage from the Philippine Health Insurance Corporation. The National Center for Disease Prevention and Control-Degenerative Disease Office (2014), developed clinical pathway guidelines for selected non-communicable diseases including cancer in the hope to manage these cases systematically in the country. All these policies and laws are meant to provide a sustainable healthcare in the Philippines but unless properly implemented, followed and financed, the realization of these dreams will remain elusive. There is nevertheless a glimmer of hope with the newly signed law last July 23, 2017, the Executive Order 26, known as the National Tobacco Ban which prohibits smoking in all public places and utility vehicles nationwide. If implemented properly, it would significantly decrease lung cancer incidence and mortality in the country.
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MS 12.05 - Sustainable Care System in South America (ID 7700)
12:00 - 12:15 | Presenting Author(s): Eduardo Richardet
- Abstract
Abstract not provided
Author of
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MA 16 - Mediastinal, Tracheal and Esophageal Tumor: Multimodality Approaches (ID 675)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Thymic Malignancies/Esophageal Cancer/Other Thoracic Malignancies
- Presentations: 1
- Moderators:K. Shibuya, Francoise Mornex
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 313 + 314
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MA 16.04 - Phase II Trial of S-1 Treatment as Palliative-Intent Chemotherapy for Previously Treated Advanced Thymic Carcinoma (ID 8627)
16:00 - 16:05 | Author(s): Yasushi Goto
- Abstract
- Presentation
Background:
Thymic carcinoma (TC) is a rare cancer with minimal evidence of survival with palliative-intent chemotherapy. Sunitinib and everolimus monotherapies have been proposed as active molecular-targeted approaches based on phase II (Ph II) trials, and S-1, an oral fluoropyrimidine, has been described in the NCCN guideline as an active cytotoxic agent for refractory TC based on a case series. Therefore, we conducted a Ph II trial to study the result of S-1 treatment in patients with refractory TC.
Method:
In this Ph II study performed at three cancer centers in Tokyo, we aimed to enroll 26 TC patients previously treated with platinum-based chemotherapy. The patients received S-1 orally twice daily at a dose of 40–60 mg/m2 for 4 weeks, followed by 2 weeks off until progressive disease or unacceptable toxicities. S-1 was used off-label. The primary end-point was determining the objective response rate, and secondary endpoints were progression-free survival (PFS), overall survival (OS), and toxicities.
Result:
Twenty-six patients (10 males) were recruited between November 2013 and May 2016. The median age was 63 (27–74) years. Among the 26 patients, 23 had squamous cell carcinoma histology and 10 had an ECOG performance status of 0. Additionally, one patient showed complete response and seven patients showed partial responses, resulting in a 30.8% response rate (95% confidence interval [CI], 16.5–50.0) and a 65.4% disease control rate (95% CI, 46.2–80.6). After a median follow-up of 13.4 months, the median PFS was 4.3 months (95% CI, 2.3–7.6 months) and median OS was 23.4 months (95% CI, 12.8–not reached). Treatment-related adverse events (AEs) of grade ≥3 included neutropenia (12%), skin rash (8%), elevated ALT, decreased WBC count, and fatigue (4%). No treatment-related death was observed. However, treatment was discontinued in three patients (12%) because of AEs.
Conclusion:
S-1 for refractory TC confirmed clinical activity with good tolerability. Clinical trial identification: UMIN000010736
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.01 - A Phase II Study of Nivolumab: A Multicenter, Open-Label, Single Arm Study in Malignant Pleural Mesothelioma (MERIT) (ID 9111)
11:00 - 11:05 | Presenting Author(s): Yasushi Goto
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy with poor prognosis and limited treatment options beyond progression after platinum-based combination with pemetrexed chemotherapy. Nivolumab (anti-PD-1, ONO-4538, BMS-936558), a humanized monoclonal antibody, PD-1 immune-checkpoint inhibitor, has demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Here, we report the preliminary results of a phase II study to evaluate the efficacy and safety of Nivolumab in previously treated Japanese MPM patients (pts): ONO-4538-41/JapicCTI-No.163247.
Method:
This open-label study enrolled advanced or metastatic MPM pts previously treated with up to two regimens of chemotherapy including platinum-based combination therapy with pemetrexed. Enrollment criteria also included histologically-confirmed, unresectable MPM without prior surgery, measurable disease and ECOG performance status 0-1. There was no restriction of PD-L1 status. Pts received Nivolumab 240 mg flat dose Q2W until progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) (modified RECIST by independent review committee, expected response rate was 19.2%); secondary endpoints included disease control rate (DCR), duration of response, progression-free survival (PFS), and overall survival (OS).
Result:
From July to October 2016, 34 pts were enrolled in 15 centers. Males: 85.2%, median age: 68.0 years (range 43-78), PS 1: 61.8%, epithelial/sarcomatoid/biphasic: 79.4%/8.8%/11.8%, 1 prior regimen: 70.6%. Median follow-up was 6.7 months. Independent review committee-assessed 6-month ORR was 29.4% (n=10, 95%CI: 16.8-46.2) and objective responses were observed across tissue types, epithelioid 7/27 (25.9%), sarcomatoid 2/3 (66.7%), biphasic 1/4 (25.0%). 13 pts (38.2%) had stable disease, resulting in a 6-month DCR of 67.6%. Median PFS was 6.1 months (95%IC: 2.9-NR). Median OS has not been reached. 6-month PFS and OS rates are 50.9% (95%CI: 32.7-66.5) and 85.3% (95%IC: 68.2-93.6). 23 (67.6%) pts experienced drug-related adverse event (DRAE), and 7 (20.6%) experienced grade 3/4 DRAEs. 2 pts required dose discontinuation because of pneumonitis (Grade2 and 3).
Conclusion:
Single-agent Nivolumab has significant activity in 2[nd]/3[rd] line MPM pts and met the primary endpoint, suggesting that Nivolumab has a potential to be a new therapeutic option for MPM.
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P1.03 - Chemotherapy/Targeted Therapy (ID 689)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-004 - Alectinib for Patients with ALK Rearrangement–Positive Non–Small Cell Lung Cancer and a Poor Performance Status (ID 8115)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
Alectinib is a potent and highly selective inhibitor of the tyrosine kinase ALK and has shown marked efficacy and safety in patients with ALK rearrangement–positive non–small cell lung cancer (NSCLC) and a good performance status (PS). It has remained unclear whether alectinib might also be beneficial for such patients with a poor PS.
Method:
Eligible patients with advanced ALK rearrangement–positive NSCLC and a PS of 2 to 4 received alectinib orally at 300 mg twice daily. The primary end point of the study was objective response rate (ORR), and the most informative secondary end point was rate of PS improvement. Plasma concentrations of alectinib were measured by liquid chromatography-mass spectrometry (LC-MS/MS).
Result:
Between September 2014 and December 2015, 18 patients were enrolled in this phase II study (Lung Oncology Group in Kyushu 1401). Twelve, five, and one patients had a PS of 2, 3, or 4, respectively, whereas four patients had received prior crizotinib treatment. The median follow-up time for all patients was 9.8 months (range, 5.6 to 18.0 months) at the time of the primary analysis. The ORR was 72.2% (90% confidence interval [CI], 52.9–85.8%), and the disease control rate was 77.8% (90% CI, 58.7–89.6%). The ORR did not differ significantly between patients with a PS of 2 and those with a PS of ≥3 (58.8% and 100%, respectively, P = 0.114). The PS improvement rate was 83.3% (90% CI, 64.8–93.1%, P < 0.0001), with the frequency of improvement to a PS of 0 or 1 being 72.2%. The median progression-free survival (PFS) was 10.1 months (95% CI, 7.1 to17.8 months), with no difference between the patients with a PS of 2 and those with a PS of ≥3 (median PFS, 10.1 and 17.8 months, respectively, P = 0.24). Toxicity was mild, with the frequency of adverse events of grade ≥3 being low. Neither dose reduction nor withdrawal of alectinib because of toxicity was necessary. The trough concentration of alectinib in plasma was 235 ± 65 ng/mL (mean ± SD), which is slightly lower than that previously reported in patients with a good PS, supporting the tolerability of alectinib administration in those with a poor PS.
Conclusion:
Alectinib is a treatment option for patients with ALK rearrangement–positive NSCLC and a poor PS. Updated data and that for overall survival will be available at presentation.
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P2.03 - Chemotherapy/Targeted Therapy (ID 704)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Chemotherapy/Targeted Therapy
- Presentations: 3
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-036 - Comparing the Efficacy/Toxicity of Osimertinib and First Line EGFR-TKI by Individual Patient Analysis (ID 9380)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
Osimertinib is a third generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), which showed its efficacy for T790M resistant mutation in patients with advanced and recurrent non small cell lung cancer (NSCLC). The efficacy and toxicity of osimertinib comparing to previous EGFR-TKIs are not fully elucidated. Since every patient receiving osimertinib has received previous EGFR-TKI therapy, we compared the efficacy and toxicity of those agents in the same patients.
Method:
We retrospectively reviewed medical records of patients with T790M mutation positive advanced and recurrent NSCLC, who had disease progression after previous EGFR-TKI, the standard first line therapy, and started osimertinib between April 2016 and March 2017 at National Caner Center Hospital. Progression free survival (PFS) of osimertinib, and 1st line EGFR-TKI PFS of the same patients were calculated by Kaplan-Meier method. Objective response rate (ORR) was assessed according to RECIST version 1,1. Adverse events (AEs) were also reviewed to evaluate the difference of safety profiles between osimertinib and previous EGFR-TKIs.
Result:
A total of 46 patients with T790M positive NSCLC received osimertinib after the failure of first line EGFR-TKI treatment. At May 2017, the median follow-up time since the start of osimertinib was 7.8months. The median age was 65 (range 36-82), the median number of treatment received before osimertinib was 3 (range 1-9), and the median wash out time of 1st line EGFR-TKI till the start of osimertinib was 14.0 months. The median PFS of osimertinib is not reached. The median PFS of first line EGFR-TKI was 15.2 months. ORR of osimertinib and first line EGFR-TKI was 56.0% and 65.2%, respectively. The most frequent AEs of any grade of osimertinib were rash, dry skin, paronychia, and diarrhea (39.4%, 35.8%, 32.1%, and 30.2%, respectively). Rash, paronychia, and diarrhea over grade 2 was 6.5%, 6.5%, and 0% with osimertinib, compared to 0%, 12.5%, and 4.1% with gefitinib, and 41.7%, 8.3%, and 0% with erlotinib. The incidence of pneumonitis with osimertinib treatment was 10.9% (5 cases) in any grade, and 6.5% (3 cases) in grade 3 to 4, though 2 of them (1 case in grade 1 and 1 in grade 3) had received nivolumab as the prior chemotherapy. Except for pneumonitis, there was no AE leading to permanent discontinuation related to osimertinib.
Conclusion:
Osimertinib showed the efficacy and feasibility even in practical use. Adverse effect of osimertinib was generally better tolerated than previous EGFR-TKIs, except for pneumonitis.
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P2.03-046 - Lymhocyte-To-Monocyte Ratio and Mean Platelet Volume as Prognostic Factor in EGFR Mutant NSCLC Treated with EGFR TKI (ID 9738)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
EGFR mutation is a strong predictor of the response to EGFR-TKI, but 10-30% of EGFR-TKI naive patients do not respond to the first line EGFR TKI therapy. Inflammation plays an important role in the initiation, progression, invasion and metastasis of cancer. Recentry study has demonstrated that hematological markers of inflammation such as LMR (lymphocyte to monocyte ratio), RDW (red cell distribution width), and MPV (mean platelet volume) are valuable biomarker in various types of human cancers. The purpose of the present study is to analyze whether hematological markers of inflammation is a prognostic factor in EGFR mutant NSCLC treated with EGFR TKI.
Method:
We retrospectively analyzed 75 advanced or recurrent NSCLC patients with common EGFR mutation treated with EGFR-TKI between 2008 to 2017 at the University of Tokyo hospital. Patients with de novo T790M mutaion, systemic corticosteroids or active infection were excluded from the analysis. We analyzed whether the hematological markers of inflammation before the TKI therapy impact the PFS of TKI therapy. The following variables were included: LMR, RDW, MPV, EGFR mutation subtype (Exon19 deletion of L858R) , ECOG performance status, age and gender. The PFS was estimated by the Kaplan-Meier method and were compared by the log-rank test. Prognostic factors for PFS were assessed by Cox’s proportional hazards regression model. Statiscital analysis was performed using the survival package in the R software.
Result:
Low LMR and high MPV were associated with shoter PFS (log-rank test, p=0.000057 and p=0.03 respectively), but RDW was not associated with PFS. In the multivariate analysis, low LMR (hazard ratio (HR) 2.9; p=0.00015), high MPV (HR 1.7; p=0.039), and poor PS (HR 2.0; p=0.046) were independent risk factors for shoter PFS.
Conclusion:
Low LMR and high MPV are independent risk factors for shorter PFS in patients treated with EGFR-TKI.
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P2.03-048 - Mixed Response of Non-Small Cell Lung Cancer Harboring the EGFR T790M Mutation to Osimertinib (ID 9807)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
Although patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations respond well to EGFR tyrosine kinase inhibitors (TKIs), most progress after approximately 1 year. At the time of progression, the EGFR T790M mutation is detected in more than half of these tumors. NSCLC harboring the T790M mutation shows a high response rate to osimertinib. However, the heterogeneous nature of NSCLC may limit the efficacy of osimertinib to those lesions with the T790M mutation, and a subset of patients may show a mixed response (MR), whereby some lesions shrink while others progress at the first evaluation. Previous study showed that about 20% of NSCLC patients exhibit MR to systemic therapies including EGFR-TKI. However, little is known about characteristics of MR to osimertinib.
Method:
To determine the frequency of a MR, we retrospectively reviewed patients treated with osimertinib for NSCLC harboring the EGFR T790M mutation at the National Cancer Center Hospital.
Result:
Between April and December 2016, 45 patients (median age 65 [36‒82] years, 19 [42%] males) who had NSCLC with the T790M mutation received osimertinib. The median numbers of previous chemotherapies and EGFR-TKI therapies received by the patients were 1 and 2, respectively. All measurable tumor lesions showed a response to therapy in 35 (77%) patients and progression in three (7%) patients. A MR was seen in seven (16%) patients. Of these seven patients, the re-biopsy specimens in which T790M was detected were derived from the primary lesion in six and a metastatic lymph node in one patient. Two types of MRs were seen among these seven patients: (1) the tumor including the re-biopsy site responded, while the other lesions progressed (five patients), and (2) the tumor including the re-biopsy site progressed (two patients). The most frequent progressive sites were liver and lung metastasis (four patients, respectively). Three patients continued to receive osimertinib after the MR, one of whom underwent drug-eluting bead transarterial chemoembolization (DEB-TACE) for progressive liver metastasis and achieved disease control on osimertinib for an additional 4 months after the MR.
Conclusion:
A MR to osimertinib was seen in 16% of patients with NSCLC harboring the EGFR T790M mutation. This suggests that resistance mechanism of 1st line EGFR-TKI may differ by the site in same patient. Since benefit of osimertinib is mainly seen in T790M mutation, addition of local therapy may be beneficial for patients who develop a MR to osimertinib.
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P2.07 - Immunology and Immunotherapy (ID 708)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Immunology and Immunotherapy
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.07-011 - Long Follow up from Phase I Study of Nivolumab and Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer (ID 8156)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
This phase I study investigated the tolerability, safety and pharmacokinetics of nivolumab in combination with chemotherapy in Japanese patients with advanced non-small-cell lung cancer (NSCLC).
Method:
Patients who have stage IIIB without indication for definitive radiotherapy, stage IV，or recurrent NSCLC were eligible. nivolumab (10 mg/kg，day 1) and chemotherapy [arm A: cisplatin (80 mg/m[2], day 1) / gemcitabine (1250 mg/m[2], day 1 and 8), arm B: cisplatin (75 mg/m[2], day 1) / pemetrexed (500 mg/m[2], day 1), arm C: carboplatin (AUC 6, day 1) / paclitaxel (200 mg/m[2], day 1) / bevacizumab (15 mg/kg, day 1), arm D: docetaxel (75 mg/m[2], day 1)] were administered every three weeks. Arm A and B were administrated for four cycles and arm C was for four to six cycles as first-line chemotherapy. After that, nivolumab in arm A, nivolumab / pemetrexed in arm B, and nivolumab / bevacizumab in arm C were continued every three weeks as maintenance therapy until disease progression. Arm D were administrated until disease progression as second-line chemotherapy.
Result:
Six patients each in four arms, total 24 patients were enrolled. Median follow-up time was 20.4 months. Progression free survival [median (range)] were 6.3 (0.7-42.2+) months in arm A, 11.8 (1.4-47.4+) months in arm B, 40.7 (5.3-43.5+) months in arm C, and 3.2 (1.9-10.9) months in arm D. Three-year progression-free survival rates were 20% in arm A, 16,7% in arm B, 62.5% in arm C, and 0% in arm D.
Conclusion:
nivolumab 10 mg/kg showed acceptable toxicity profile and encouraging antitumor activity in combination with chemotherapies in Japanese patients with advanced NSCLC. Especially, arm C showed favorable response rate and long progression free survival in this study.
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P3.02 - Biology/Pathology (ID 620)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Biology/Pathology
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.02-041 - EGFR Amplification Mediates Resistance to TAS121, A Third-Generation EGFR-TKI, in EGFR T790M-Positive Non-Small Cell Lung Cancer (ID 9168)
09:30 - 09:30 | Author(s): Yasushi Goto
- Abstract
Background:
Third-generation epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) have shown promising efficacy in EGFR T790M-mutation-positive non-small cell lung cancer (NSCLC). However, acquired resistance to third-generation EGFR-TKIs has been reported in EGFR T790M-positive NSCLC. The mechanism of resistance to these third-generation EGFR-TKIs has not been fully elucidated. We report a case of metastatic NSCLC harboring an EGFR T790M mutation in which EGFR amplification mediated acquired resistance to TAS121, a novel third-generation EGFR-TKI.
Method:
A 68-year-old woman with metastatic lung adenocarcinoma, harboring an EGFR L858R mutation, received gefitinib in September 2013. Although the patient achieved a partial response, the tumor progressed and she was treated with 4 cycles of chemotherapy using cisplatin and pemetrexed followed by pemetrexed maintenance therapy. In April 2015, computed tomography (CT) showed disease progression (PD) with liver metastases, and re-biopsy of hepatic lesions was performed. Tumor genotyping with the PNA LNA PCR-Clamp method revealed an original mutation of EGFR L858R in exon 21 and a secondary mutation of EGFR T790M in exon 20. Tumor progression was noted after completion of one cycle of docetaxel, and she was enrolled into a phase 1 trial of TAS121 in June 2015. Although she showed a partial response to TAS121, PD was confirmed on CT, which indicated progression of liver metastases. She discontinued TAS121 and received supportive care. She died in October 2015, and an autopsy was performed. To determine the mechanism of resistance to TAS121, we performed next-generation sequencing (NGS) (NCC OncoPanel, Agilent) with post-TAS121 samples obtained from progressing liver lesions during TAS121 treatment. We also conducted fluorescence in situ hybridization (FISH) analysis for EGFR in pre-TAS121 liver lesions, post-TAS121 liver lesions, and autopsy samples from the lung and liver. The study protocol was approved by the Ethical Review Committee of the National Cancer Center Hospital.
Result:
NGS with the post-TAS121 liver samples showed EGFR amplification in the tumor cells (log2 ratio 2.2). On FISH analysis, EGFR amplification was not detected in the pre-TAS121 liver lesions (the ratio of EGFR signals to CEP signals 1.7), but was detected in the post-TAS121 liver lesions (2.1) and those obtained at autopsy (3.0). EGFR amplification was not detected in the autopsy samples of the lung lesions (1.0), which remained stable during TAS121 treatment.
Conclusion:
Our case revealed that genomic instability of the EGFR domain contributed to the development of resistance to TAS121. Further molecular analysis is warranted to understand the role of EGFR amplification in acquired resistance to third-generation EGFR-TKIs.
