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Kenichiro Kudo
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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 - 16:00 | Author(s): Kenichiro Kudo
- 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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P2.01 - Advanced NSCLC (ID 618)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:00 - 16:00, Exhibit Hall (Hall B + C)
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P2.01-034 - Phase I/II Trial of Weekly Nab-Paclitaxel as 2nd or 3rd Line Treatment in NSCLC Without Driver Mutations. (OLCSG1303) (ID 9275)
09:00 - 16:00 | Presenting Author(s): Kenichiro Kudo
- Abstract
Background:
Although nab-paclitaxel (PTX) plus carboplatin is one of the standard treatment for chemo-naive advanced non-small cell lung cancer (NSCLC), the efficacy, safety and optimal schedule of nab-PTX monotherapy as 2nd or 3rd line for NSCLC patients without any driver mutations remains unknown.
Method:
This was a single arm phase I/II study. Eligible patients are advanced NSCLC without EGFR mutation and ALK rearrangement that progressed after platinum-doublet chemotherapy. The patients were received 100mg/m[2] of nab-PTX on day 1, 8, 15 and 22 (level 0) or on day 1, 8, and 15 (level -1) every 4-week in the phase I portion. Dose limiting toxicities (DLT) was assessed and the recommended schedule was determined. The primary endpoint was objective response rate (ORR), assuming that estimated ORR was 15% and threshold ORR was 5% with α error of 0.05 and β error of 0.2 in the phase II part. Total of 55 patients were planned to be enrolled.
Result:
The recommended schedule of nab-PTX was determined as the level -1, because the DLTs were found in 4 of 5 patients. The characteristics of the 55 patients enrolled in the phase II were as followings; median age, 66 years (range, 41–90 years), male/female=40/15, PS 0/1/2=12/39/4, 2nd/3rd line=34/21, adeno/squamous/large/others=34/17/2/2. The median number of treatment cycles was three (range, 1–10). The ORR was 7.3% (95% confidence interval [CI], 2.0–17.6%; 4 PR, 26 SD, 24 PD, 1 NE). At the median follow-up time of 5.3 months (range, 1.9–26.0 months) for all patients, the median PFS was 3.4 months (95% CI, 1.9–4.0 months). Treatment related grade 3 or 4 toxicities were neutropenia (36%), febrile neutropenia (5.5%) and pulmonary infection (3.6%). Three patients (5.5%) had grade 2 pneumonitis and one patient was died due to ARDS.
Conclusion:
This study failed to meet predefined primary endpoint although PFS was comparable and toxicity was acceptable for patients with advanced NSCLC without EGFR or ALK mutation as 2nd or 3rd line treatment. (UMIN registration number: 000012404).
