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Yi Guo
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P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.14-42 - Apatinib Combined with EGFR - TKI in Treating Advanced Non-Small Cell Lung Cancer with EGFR - TKI Resistance (Data Updated) (ID 1833)
09:45 - 18:00 | Author(s): Yi Guo
- Abstract
Background
EGFR-TKI has been widely used in patients with EGFR mutations in non-small cell lung cancer (NSCLC) and gained significant benefits.But resistance to EGFR-TKI is inevitable.Previous studies have shown that apatinib (a TKI against VEGFR-2) combined with EGFR-TKI might prevent progression of the disease. We conducted this trial to investigate the efficacy and safety of apatinib combined with EGFR-TKIs(including erlotinib, gefitinib,icotinib,afatinib and osimertinib) compared with traditional chemotherapy for EGFR-TKI resistant NSCLC pts.
Method
This study enrolled 39 advanced NSCLC pts who acquired resistance to the EGFR-TKI therapy from Mar 2017 to Jan 2019. 25 pts received apatinib combined with EGFR-TKI (apatinib in start dose of 250 mg+prior EGFR-TKI dose),14 pts received chemotherapy ( pemetrexed or vinorelbine with platinum). Efficacy was evaluated every 6 weeks based on RECIST 1.1. This study was registered on Chinese Clinical Trail Registry, and the registration number was ChiCTR-OIN-17012051.
Result
In the apatinib group, 88%(22/25) pts were available evaluated. The objective response rate was 13.6%(3/22) and the disease control rate was 95.5% (21/22). The most common adverse events in the apatinib group were diarrhea (60%,15/25), hypertension (56%,14/25), hand-foot syndrome (40%,10/25), fatigue (30.4%,7/23 ). Main grade 3 or 4 toxicities were proteinuria (12%, 3/25). Two pts with brain metastases in the apatinib group got metastases lesions decreased. The lesions of two pts who have been taken the dose of 250mg apatinib and progressed had decreased when they change the dose to 500mg.
In the chemotherapy group,78.6%(11/14) pts were available evaluated. The objective response rate was 27.3%(3/11) and the disease control rate was 90.9% (10/11).None new adverse event occured.
The objective response rate and disease control rate were similar in two group, there were differences in length of treatment. The median length of treatment of apatinib group was 8.7 month，and chemotherapy group was 4.3 month.The longest treatment period in the apatinib group was 24 months.
Conclusion
Apatinib combined with EGFR-TKI shown a good clinical efficacy in pts with acquired EGFR-TKI(1st 2nd or 3rd generation) resisitance.Patient's quality of life and the compliance of therapy had been increased by oral drugs.Besides,We found that in the patients who were treated with erlotinib, or patients with EGFR 21 mutation, or male, their PFS tended to be prolonged compared to other patients.
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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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P2.14-42 - Emergence of CCDC6-RET Fusion with Maintained EGFR T790M Mutation After Resistance to Osimertinib in NSCLC: A Case Report (ID 1086)
10:15 - 18:15 | Presenting Author(s): Yi Guo
- Abstract
Background
First- and second-generation EGFR-TKIs have been widely used for advanced patients with EGFR mutation-positive non-small cell lung cancer (NSCLC); however, acquired resistance to these inhibitors, such as EGFR T790M mutation, could be present in resistant cases. Several third-generation EGFR-TKIs including osimertinib, have been explored and approved for conquering this resistance, whereas acquired resistance to osimertinib is evident and resistance mechanisms remain complex and incompletely elucidated.
Method
A 56-year-old never-smoking Asian woman presenting with back and groin pain for 2 years, and was diagnosed with stage IV lung adenocarcinoma with multiple lung, liver, brain and bone metastases in February 2015. The patient carried EGFR exon 19 deletion and clinically responded to initial erlotinib treatment, who progressed on erlotinib after 20 months, and a T790M mutation was detected by next-generation sequencing (NGS). Osimertinib treatment was administrated for 13 months during which time the patient remained stable according to the Response Evaluation Criteria in Solid Tumors. The patient progressed with bone metastases in January 2018 and no other mutations were detected by NGS, who then started the treatment with osimertinib, bevacizumab, and complementary radiation therapy. However, the patient discontinued the treatment due to the progress with bilateral lung nodules. In order to probe into the subsequent therapy, circulating tumor DNA (ctDNA) was analyzed using NGS with Acornmed Panel in August 2018.
Result
The genomic profile of the tumor disclosed actionable mutations including EGFR exon 19 deletion, EGFR T790M mutation, and CCDC6-RET fusion. Osimertinib and bevacizumab discontinued because of the rapid progress, serious adverse effects of gradeⅡsuppression of bone marrow, and shortness of breath. Based on the molecular test results, the patient received treatment with cabozantinib and osimertinib in October 2018, which also failed to slow down the progress of the disease. Further ctDNA test in November 2018 showed EGFR exon 19 deletion, EGFR T790M mutation, and CCDC6-RET fusion were identified again; however, no novel mutations were detected. Unfortunately, the symptoms worsened quickly and the patient died of respiratory failure in December 2018.
Conclusion
The specifc mechanisms of acquiring drug resistance for EGFR-TKIs have not been fully elucidated. Based on ctDNA-based NGS, we reported a case maintained EGFR T790M mutation and acquired CCDC6-RET fusion after resistance to osimertinib, which was rare since acquired RET fusion was only found in EGFR T790M lost patients. More studies about the mechanism should be explored to lead to effective treatment strategies in this population.
