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T. Ninomiya
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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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P1.03-038 - A Phase I Trial of Afatinib and Bevacizumab in Untreated Patients with Advanced NSCLC Harboring EGFR-Mutations: OLCSG1404 (ID 9704)
09:30 - 09:30 | Author(s): T. Ninomiya
- Abstract
Background:
In advanced EGFR-mutant NSCLC, afatinib, a second-generation EGFR-tyrosine kinase inhibitor (EGFR-TKI) has demonstrated a significant survival benefit over platinum-based chemotherapy (Lancet Oncol. 2015) and the combination therapies of EGFR-TKI and bevacizumab showed favorable PFS data (J Thorac Oncol. 2015 and Lancet Oncol. 2014). Also, our preclinical study revealed the synergistic effect of afatinib and bevacizumab (Mol Cancer Ther. 2013). We hypothesized afatinib and bevacizumab potentially yields further efficacy and conducted a phase I trial.
Method:
Untreated patients with advanced EGFR-mutant NSCLC were enrolled. The primary endpoint was set as safety. The first 6 patients received afatinib at 40 mg/body daily and bevacizumab intravenously at 15 mg/kg every 3 weeks until PD or unacceptable toxicity (level 0). If 2 or fewer patients experienced DLT, we repeated at the same dose to additional 6 patients. When 2 or fewer patients experienced DLT in the both sets, we concluded this dose was feasible. Otherwise, we repeated the same method at the level -1 (afatinib 30 mg/body, bevacizumab 15 mg/kg). If the dose was feasible, the level was recommended.
Result:
Nineteen patients were enrolled (level 0: 5 and level -1: 14). Three patients at level 0 experienced DLT, which concluded level 0 was unfeasible. At level -1, 3 patients developed DLT. All of the DLT soon recovered. Severe adverse events were shown in Table. Three patients at level 0 and 5 at level -1 required dose reduction for toxicity, respectively. Two patients at level 0 stopped protocol therapy for toxicity, whereas 2 at level -1 for wish of patients. Among 16 evaluable patients, the best response was CR / PR (81.3%) and SD (18.8%).
Conclusion:
Dose level -1 was well tolerated and had evidence of disease control. There was no refractory patient as well as other trials of EGFR-TKI plus bevacizumab.Level 0 (n=5) Level -1 (n=14) Grade 4 0 0 Grade 3 5 4 Grade 3 (* DLT) Diarrhea 2[*] 2[*] Skin rash 1 1 Hypoxia 1[*] 0 Anorexia 0 1[*] Paronychia 1 0
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-088k - Significance of Second Rebiopsy for Detecting T790M Mutation (ID 8642)
09:30 - 09:30 | Author(s): T. Ninomiya
- Abstract
Background:
Osimertinib is an essential drug for the treatment of non-small cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) T790M mutation and rebiopsy is recommended for detecting T790M. However, significance of repeating rebiopsy in NSCLCs that were T790M negative with first rebiopsy remains unclear. Here, we sought to clarify this issue using a retrospective cohort.
Method:
We reviewed the medical records of patients with consecutive advanced NSCLC harboring activating EGFR mutations who underwent EGFR tyrosine kinase inhibitor (TKI) at Okayama University Hospital between Jan 2015 and Jan 2017.
Result:
In total, 104 patients were included in this study, and 47 patients underwent rebiopsy after acquiring resistance to prior EGFR TKIs. Preexisting activating EGFR mutations were found in all the 47 rebiopsied samples. Nineteen of them were T790M positive (40%). In the remaining 28 patients (T790M negative with first rebiopsy), 18 patients underwent additional rebiopsies following to interval therapies. Eleven (61%) of them were T790M positive with 2nd/3rd rebiopsy (10 with 2nd rebiopsy and 1 with 3rd rebiopsy). In majority of the 11 patients, rebiopsied samples were obtained from different lesions between first and 2nd/3rd rebiopsy (8/11, 73%). We also evaluated the efficacy of osimertinib in the 11 patients who needed 2nd/3rd rebiopsy for detecting T790M. Osimertinib showed good activity with the objective response rate 56% and the median progression free survival 5.5 months (95% confidence interval 4.1-6.9), though it is worse compared to with historical control osimertinib therapy.
Conclusion:
T790M could be found even in T790M negative NSCLCs with first rebiospy. Data will be updated at the meeting.
