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Satoshi Watanabe
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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: 3
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-010 - Updated Survival Outcomes of NEJ005/TCOG0902, a Randomized PII of Gefitinib and Chemotherapy in EGFR-Mutant NSCLC (ID 7948)
09:30 - 16:00 | Author(s): Satoshi Watanabe
- Abstract
Background:
North East Japan Study Group (NEJ) 005/ Tokyo Cooperative Oncology Group (TCOG) 0902 study has demonstrated that first-line concurrent (C) and sequential alternating (S) combination therapies of EGFR tyrosine kinase inhibitor (gefitinib) plus platinum-based doublet chemotherapy (carboplatin/pemetrexed) offer promising efficacy with predictable toxicities for patients with EGFR-mutant NSCLC (ASCO2014, Ann Oncol 2015). However, overall survival (OS) data were insufficient because of the lack of death events in the primary report.
Method:
Progression-free survival (PFS) and OS were re-evaluated at the final data cutoff point (March 2017) for the entire population (N = 80).
Result:
At the median follow-up time of 35.6 months, 88.8% of patients had progressive disease and 77.5% of patients had died. Median PFS was 17.5 months for the C regimen and 15.3 months for the S regimen (p = 0.13). Median OS time was 41.9 with the C regimen and 30.7 months with the S regimen (p = 0.036). Updated response rates were similar in both groups (90.2% and 82.1%, respectively; p = 0.34). Patients who had common mutations showed no significant differences in PFS according to type of mutation. Patients with Del19 displayed relatively better OS (median: 45.3 and 33.3 months for C and S regimens) than those with L858R (31.4 and 28.9 months). No severe adverse events including interstitial lung disease have occurred during the follow-up period since the primary report. In an exploratory analysis, there was no significant difference in post progression survival and overall survival between patients with progression of target or non-target lesions and those progressed with new lesions.
Conclusion:
This updated analysis has confirmed that PFS is improved with first-line combination therapies compared to that with gefitinib monotherapy, and the C regimen in particular offers an overall survival benefit of 42 months in the EGFR-mutated setting. Our on-going NEJ009 study will clarify whether this combinational strategy can be incorporated into routine clinical practice.
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P2.03-015 - Efficacy of EGFR-TKIs for EGFR Mutatnt NSCLC Patients with Central Nervous System Metastases: A Retrospective Analysis (ID 8297)
09:30 - 16:00 | Author(s): Satoshi Watanabe
- Abstract
Background:
Central nervous system (CNS) is a common site of metastases of non-small cell lung cancer (NSCLC). The prognosis for patients with brain metastases and/or leptomeningeal metastases is extremely poor. NSCLC harboring epidermal growth factor receptor (EGFR) mutation generally shows good response to tyrosine kinase inhibitors (TKI). However, the efficacy of EGFR-TKI in patients with CNS metastases is unclear. And the data on the occurrence of leptomeningeal metastases in the patients with brain metastases after use or EGFR-TKI remain limited.
Method:
We retrospectively evaluated clinical outcome and background of EGFR mutant NSCLC patients with CNS metastases who received EGFR-TKI for the first line drug therapy between January 2008 and December 2014 in the facilities belong to Niigata lung cancer treatment group.
Result:
A total of 104 eligible patients were enrolled. The response rate was 62%. The median time to treatment failure was 7.8 months. The median survival time (MST) was 24.0 months. The response rate of CNS was 37%. The median CNS-progression free survival (PFS) was 13.2 months. There was no statistical significant difference in TTF, overall survival (OS) and CNS-PFS between patients with exon 19 deletion and those with exon 21 L858R point mutation (mTTF 8.3 vs. 7.8 months, MST 26.1 vs. 24.9 months, mCNS-PFS 14.4 vs. 12.4 months) or between patients treated by Gefitinib and those treated by Erlotinib (mTTF 8.4 vs. 6.3 months, MST 26.0 vs. 20.2 months, mCNS-PFS 13.8 vs. 13.2months). Brain radiotherapy prior to EGFR-TKI prolonged TTF (11.2 vs. 6.8 months) and tended to prolong CNS-PFS (15.6 vs. 11.1 months), but was not significantly associated with OS (MST 26.1 vs. 24.0 months). There was no significant difference in treatment outcome between patients who received stereotactic irradiation and those who received whole brain irradiation as brain radiotherapy prior to EGFR-TKI. Leptomeningeal metastases (LM) were primarily found in 8 of 104 patients (8%), and those occurred subsequently during the clinical course in 19 patients (18%). Median time to occurrence of LM in the patients who had LM subsequently was 14.5 months. There was no significant difference in OS between patients who had LM subsequently and those without LM during the course (MST 28.1 vs. 24.9 months). MST from diagnosis of subsequent LM was 3.7 months.
Conclusion:
EGFR-TKI showed favorable effect for EGFR mutant NSCLC patients with CNS metastases. A longer TTF and CNS-PFS were observed with prior brain radiotherapy. Prognosis after occurrence of LM was poor.
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P2.03-021 - A Phase I Study Evaluating the Combination of Afatinib, Carboplatin and Pemetrexed after Failure of 1<Sup>St</Sup> Generation EGFR-TKIs (ID 8713)
09:30 - 16:00 | Author(s): Satoshi Watanabe
- Abstract
Background:
Despite the high response rate in patients with EGFR-mutation positive NSCLC, treatment with EGFR-TKIs is not curative and eventually there is disease progression. In patients with acquired resistance to 1[st] generation EGFR-TKIs, previous studies have demonstrated that afatinib had some clinical activity. We previously reported that the combination of gefitinib, pemetrexed and carboplatin showed promising antitumor efficacies in EGFR-mutated lung cancer patients. In this phase I trial, we assessed the safety and efficacy of afatinib combined with pemetrexed and carboplatin in NSCLC patients who acquired resistance.
Method:
Patients with EGFR-mutation positive metastatic NSCLC, who had received 1[st] line gefitinib or erlotinib and developed disease progression were eligible. Patients received pemetrexed 500 mg/m[2] and carboplatin AUC=5 on day 1 in all cohorts, and afatinib at doses of 20, 30 and 40 mg/body from day 8 to 18 of 21-day cycle. DLT was assessed after the first cycle, and doses were escalated in cohorts of 3 to 6 patients.
Result:
Eleven patients were enrolled to this trial and 9 patients were evaluable for safety and efficacy. At an afatinib dose of 30mg/body, 3 patients experienced DLT (grade 3 diarrhea, grade 3 hypokalemia, grade 4 thrombocytopenia, grade 3 amylase elevation and grade 3 gamma-glutamyl transferase). The overall response rate was 20% (95% C.I. 5.7 to 51) and median progression free survival was 16.2 months (95% C.I. 4.7 to not reached).
Conclusion:
The MTD of afatinib is 20mg/body in combination with pemetrexed 500 mg/m[2] and carboplatin AUC=5 on day 1 every 21 days. This combination demonstrated activity in EGFR mutation positive NSCLC with acquired resistance to 1[st] line EGFR-TKIs.
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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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P2.07-007 - Retrospective Analysis of Antitumor Effects and Biomarkers of Nivolumab in NSCLC Patients with EGFR Mutations (ID 7988)
09:30 - 16:00 | Presenting Author(s): Satoshi Watanabe
- Abstract
Background:
Randomized phase III trials demonstrated that nivolumab was significantly more efficacious than docetaxel in previously treated NSCLC patients; however, subgroup analysis indicated that nivolumab had no superior antitumor effects in patients with EGFR mutations. Recent studies have shown that predictive biomarkers, such as PD-L1 expression on tumor cells and infiltration of CD8[+] T cells into tumor tissues, were associated with response to nivolumab. The present study was conducted to evaluate the antitumor effects and biomarkers of nivolumab in NSCLC patients with EGFR mutations.
Method:
We retrospectively assessed 8 EGFR-mutated NSCLC patients treated with nivolumab.
Result:
All patients had adenocarcinoma histology. Six patients had 19 deletion, 1 had L858R and 1 had S768I point mutations. During nivolumab treatment, no patients achieved partial response and stable disease. Seven patients had progressive disease and 1 was not evaluable. The median number of cycles was only 2. The median progression free survival and median overall survival from the beginning of nivolumab was 32 days (95% C.I. 7 to 51) and 370 days (95% C.I. 230 to 480). PD-L1 expression (28-8 pharmDx) was observed in 3/2/1 patients before the start of nivolumab using cutoffs of >1%, >5% and >50% tumor cell staining. Immunohistochemistry revealed that CD4[+] and CD8[+] tumor infiltrating lymphocytes were observed in all patients before nivolumab.
Conclusion:
The current study indicated that nivolumab was not effective in patients with EGFR mutations regardless of predictive biomarkers of nivolumab.
