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Daijiro Harada
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MA 07 - ALK, ROS and HER2 (ID 673)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:Robert C. Doebele, J.C. Ho
- Coordinates: 10/17/2017, 15:45 - 17:30, Room 316
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MA 07.11 - A Phase II Study of Trastuzumab Emtansine in HER2-positive Non-Small-Cell-Lung Cancer (ID 8453)
15:45 - 17:30 | Presenting Author(s): Daijiro Harada
- Abstract
- Presentation
Background:
Trastuzumab emtansine (T-DM1), an anti-HER2 antibody conjugated with vinca-alkaloid, has been approved for clinical use in HER2-positive breast cancer. HER2-alterations are detected even in non-small-cell lung cancer (NSCLC). We have launched a phase II trial of T-DM1 monotherapy for patients with HER2-positive lung cancer.
Method:
Eligible patients had pathologically diagnosed NSCLC with documented HER2-positivity (immunohistochemistry [IHC] 3+, both IHC 2+ and fluorescence in situ hybridization [FISH] +, or exon 20 insertion mutation) and were previously treated with standard chemotherapy. Thirty patients would receive T-DM1 3.6 mg/kg every 3 weeks. The primary endpoint is the overall response rate (ORR) per RECIST v1.1.
Result:
This study was early terminated due to the limited efficacy, leading that only 16 patients were registered. The demographics of the 15 evaluable patients were as follows: age (median; 67, range: 45-77), sex (male; 47%), performance status (0-1; 80%), histology (non-squamous; 100%), HER2 status (IHC3+; 33%, IHC2+/FISH; 20%, and mutation; 47%) and number of prior chemotherapeutic regimens (median; 4, range: 1-7). Of 15 patients, one, who possessed HER2 mutation achieved a partial response, resulting in ORR of 6.7%. None of the 15 patients experienced treatment-related deaths. Survival data would be presented at the meeting.
Conclusion:
T-DM1 has a limited efficacy for HER2-positive NSCLCs in our cohort. Additional molecular approaches are warranted for the precision medicine in HER2-positive tumors. UMIN registration number 000019446.
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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): Daijiro Harada
- 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 | Author(s): Daijiro Harada
- 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).
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P2.05 - Early Stage NSCLC (ID 706)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Early Stage NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.05-009 - Outcome of Stereotactic Body Radiotherapy for Clinical Stage I Non Small Cell Lung Cancer and CT Findings: Comparison with Surgical Resection (ID 9964)
09:30 - 16:00 | Author(s): Daijiro Harada
- Abstract
Background:
The standard care for Stage I non small cell lung cancer (NSCLC) is surgical resection, but stereotactic body radiotherapy (SBRT) can be an alternative treatment option, especially for patients with comorbidities. However, it is difficult to compare the outcomes of SBRT with surgical resection because their characteristics are so different, and the risk factors for recurrence after SBRT are not fully understood. In this study, we report pretreatment clinical characteristics and CT findings in patients treated with SBRT, and reviewed patients underwent surgery with similar tumors.
Method:
Between January 2012 and December 2015, patients treated with SBRT for cT1-2N0M0 NSCLC and 218 patients who underwent surgery for cT1b-2N0M0 NSCLC in our institution were analyzed.
Result:
During the study period, 88 patients were treated with SBRT. The 3-year disease free survival (3-year DFS) for all patients was 81.2%. There were 15 cases of recurrences (9 cases of lymph node recurrences, 8 cases of distant metastases and 2 cases of local recurrence. 4 cases were both lymph node and distant metastases). There was no recurrence among the patients with no more than 1cm of consolidation (cT1a or less according to the 8th edition of the Union for International Cancer Control TNM classification) and all recurrent cases were with solid pattern predominant tumors (maximum consolidation diameters were more than 50% of tumor diameters) based on CT findings. Then we evaluated outcomes and clinical characteristics of patients who were treated with SBRT or underwent surgery for cStage I, cT1b or more and solid predominant NSCLC during the same period. 61 patients were treated with SBRT and 218 underwent surgery (190 cases of lobectomy, 21 secmentectomy and 7 wedge resection). Among clinical characteristics, smaller tumor sizes tend to be treated with SBRT (average sizes were 2.25 and 2.57 cm respectively, p=0.055). The mean age was significantly higher in SBRT group (78.5 vs 68.0, p<0.001). Surgical resection was associated with improved DFS (3-year DFS 84.4% vs 73.4%, p=0.004) and lymph node metastasis was found in 34 cases (15.6%) pathologically in patients underwent surgery, suggesting they are incurable with SBRT.
Conclusion:
The main limitations of this study are the small number of cases and different patient characteristics. Taken together, our data suggesting SBRT is acceptable for patients with cT1a or less, cStage I NSCLC, and surgical resection is recommended for patients with more advanced NSCLC.
