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S. Murakami
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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: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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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): S. Murakami
- 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): S. Murakami
- 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.
