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Shoichi Kuyama
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OA 12 - Emerging Genomic Targets (ID 679)
- Event: WCLC 2017
- Type: Oral
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:H. Akita, Maurice Pérol
- Coordinates: 10/18/2017, 11:00 - 12:30, F203 + F204 (Annex Hall)
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OA 12.03 - Clinical Features of Advanced Lung Cancer Harboring HER2 Aberrations: A Large Prospective Cohort Study (HER2-CS STUDY) (ID 8694)
11:20 - 11:30 | Author(s): Shoichi Kuyama
- Abstract
- Presentation
Background:
HER2 is a potential driver oncogene. HER2-targeted precision therapy has been tested in NSCLC. However, the demographics of HER2-positive NSCLC have not been defined systematically.
Method:
Pts with advanced NSCLC were registered. HER2-IHC and FISH assays were performed with commercial kits. HER2 mutations were identified by the direct sequencing. The aim of this study was to clarify the frequency, characteristics and outcome of HER2-positive NSCLC.
Result:
Of 1,126 tumors screened (Table A), 34 (3.0%) were IHC3+, and 34 (3.0%) were IHC2+/FISH+. Among the 724 EGFR wild-type tumors, 21 (2.9%) were HER2-mutant tumors, including A775_G776insYVMA (n = 15). Interestingly, the IHC3+ tumors and mutant tumors were entirely exclusive. Female pts had HER2 mutant tumors more frequently, while IHC/FISH+ tumors were detected more often in males (Table B). HER2-positive tumors had similar survival outcome to triple negative tumors, but significantly worse prognoses than EGFR-mutant and ALK-positive tumors (p < 0.05 each). The treament info will be presented at the meeting.
*including 22 pts with HER2-positive tumors with EGFR mutations, 2 with both HER2- and ALK-positive tumors, and 2 had ALK-positive tumors with EGFR-mutations. ** 1 had an IHC2+/FISH+ tumor with mutation.A. The Genotype-Specific Subsets* HER2 (n = 88) EGFR (n = 358) ALK (n = 44) Triple negative /unknown (n = 662) Total (n = 1,126) Age, median Sex (male) Smoking habit Non-Sq Stage III/IV 69 61 (69%) 58 (66%) 78 (89%) 51 (58%) 69 142 (40%) 142 (40%) 351 (98%) 220 (61%) 62 21 (48%) 19 (43%) 44 (100%) 35 (80%) 69 516 (78%) 544 (82%) 503 (76%) 423 (64%) 69 726 (64%) 754 (67%) 951 (84%) 714 (63%) MST (mo) 1-yr OS rate 17.5 59% NR 85% NR 79% 15.1 59% 19.8 67% B. The Subsets of HER2 aberrations** IHC3+ (n = 34) IHC2+/FISH+ (n = 34) Mutant (n = 21) Age, median Sex (male) Smoking habit Non-Sq Stage III/IV 71 27 (79%) 24 (71%) 30 (88%) 17 (50%) 71 27 (79%) 26 (76%) 28 (82%) 21 (62%) 65 8 (38%) 9 (43%) 21 (100%) 14 (67%) MST (mo) 1-yr OS rate 10.5 46% 16.0 70% NR 59%
Conclusion:
This is the first prospective study showing a small fraction of NSCLC possessed HER2 aberrations. HER2-positive tumors had relatively poor prognosis. NSCLCs with HER2 IHC3+ and mutation seem to be distinct subsets.
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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 | Presenting Author(s): Shoichi Kuyama
- 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 - 09:00 | Author(s): Shoichi Kuyama
- 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).
