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T. Kijima
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MA 19 - Mesothelioma: Bench to Bedside (ID 680)
- Event: WCLC 2017
- Type: Mini Oral
- Track: Mesothelioma
- Presentations: 1
- Moderators:Dean A Fennell, Hedy Lee Kindler
- Coordinates: 10/18/2017, 11:00 - 12:30, Room 315
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MA 19.01 - A Phase II Study of Nivolumab: A Multicenter, Open-Label, Single Arm Study in Malignant Pleural Mesothelioma (MERIT) (ID 9111)
11:00 - 11:05 | Author(s): T. Kijima
- Abstract
- Presentation
Background:
Malignant pleural mesothelioma (MPM) is a rare and highly aggressive malignancy with poor prognosis and limited treatment options beyond progression after platinum-based combination with pemetrexed chemotherapy. Nivolumab (anti-PD-1, ONO-4538, BMS-936558), a humanized monoclonal antibody, PD-1 immune-checkpoint inhibitor, has demonstrated antitumor activity and a manageable safety profile in several advanced malignancies. Here, we report the preliminary results of a phase II study to evaluate the efficacy and safety of Nivolumab in previously treated Japanese MPM patients (pts): ONO-4538-41/JapicCTI-No.163247.
Method:
This open-label study enrolled advanced or metastatic MPM pts previously treated with up to two regimens of chemotherapy including platinum-based combination therapy with pemetrexed. Enrollment criteria also included histologically-confirmed, unresectable MPM without prior surgery, measurable disease and ECOG performance status 0-1. There was no restriction of PD-L1 status. Pts received Nivolumab 240 mg flat dose Q2W until progression or unacceptable toxicity. The primary endpoint was the objective response rate (ORR) (modified RECIST by independent review committee, expected response rate was 19.2%); secondary endpoints included disease control rate (DCR), duration of response, progression-free survival (PFS), and overall survival (OS).
Result:
From July to October 2016, 34 pts were enrolled in 15 centers. Males: 85.2%, median age: 68.0 years (range 43-78), PS 1: 61.8%, epithelial/sarcomatoid/biphasic: 79.4%/8.8%/11.8%, 1 prior regimen: 70.6%. Median follow-up was 6.7 months. Independent review committee-assessed 6-month ORR was 29.4% (n=10, 95%CI: 16.8-46.2) and objective responses were observed across tissue types, epithelioid 7/27 (25.9%), sarcomatoid 2/3 (66.7%), biphasic 1/4 (25.0%). 13 pts (38.2%) had stable disease, resulting in a 6-month DCR of 67.6%. Median PFS was 6.1 months (95%IC: 2.9-NR). Median OS has not been reached. 6-month PFS and OS rates are 50.9% (95%CI: 32.7-66.5) and 85.3% (95%IC: 68.2-93.6). 23 (67.6%) pts experienced drug-related adverse event (DRAE), and 7 (20.6%) experienced grade 3/4 DRAEs. 2 pts required dose discontinuation because of pneumonitis (Grade2 and 3).
Conclusion:
Single-agent Nivolumab has significant activity in 2[nd]/3[rd] line MPM pts and met the primary endpoint, suggesting that Nivolumab has a potential to be a new therapeutic option for MPM.
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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: 2
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P1.03-047 - Carboplatin/ Weekly Nab-PTX in Elderly Patients with Previously Untreated Advanced Squamous NSCLC Selected Based on MNA-SF (ID 7582)
09:30 - 09:30 | Author(s): T. Kijima
- Abstract
Background:
This multicenter, single-arm, open-label, phase 2 study assessed the efficacy and safety of carboplatin plus weekly nanoparticle albumin-bound paclitaxel in elderly patients with previously untreated advanced squamous non-small-cell lung cancer, selected based on the Mini Nutritional Assessment short-form scores (MNA-SF).
Method:
Patients received carboplatin (area under the curve: 6) on Day 1, and nanoparticle albumin-bound paclitaxel (100 mg/m[2]) on Days 1, 8, and 15, every 28 days for ≤4 cycles. Eligibility criteria included an MNA-SF score of ≥8 points. The primary endpoint was the objective response rate.
Result:
Thirty patients with a median age of 76 (range, 70–83) years were enrolled. The objective response rate was 50.0% (95% confidence interval: 31.3–68.7%), which met the primary objective of this study. The disease control rate was 73.3% (95% confidence interval: 54.1–87.7%). At a median follow-up of 15.0 months, the median progression-free and overall survival was 7.1 and 19.1 months, respectively. The most common treatment-related adverse event of Grade ≥3 was neutropenia (66.7%). Non-hematological adverse events of Grade ≥3 were minor. Well-nourished patients, based on the MNA-SF, experienced fewer adverse events of Grade ≥3 compared to patients at risk of malnutrition. All treatment-related adverse events were tolerable and reversible. There were no treatment-related deaths.
Conclusion:
Carboplatin plus weekly nanoparticle albumin-bound paclitaxel is effective and well tolerated as a first-line treatment for elderly patients with advanced squamous non-small-cell lung cancer. Eligibility based on MNA-SF screening may be useful in determining acceptable toxicity.
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P1.03-049 - Phase II Study of S-1 plus Bevacizumab Combination Therapy for Patients Previously Treated for Non-Squamous Non–Small Cell Lung Cancer (ID 8008)
09:30 - 09:30 | Author(s): T. Kijima
- Abstract
Background:
The combination of platinum plus third-generation cytotoxic drugs has been the gold standard first-line chemotherapy for patients with advanced NSCLC. However, most patients experience disease progression during or after first-line treatment. The survival benefit of S-1 monotherapy as second-line therapy is not satisfactory. Bevacizumab conferred a survival benefit when combined with carboplatin and paclitaxel as first-line treatment in non-squamous NSCLC. The benefit of adding bevacizumab to non-platinum cytotoxic monotherapy such as S-1 is not clear as subsequent treatment. Therefore, we conducted a multi-center, a single-arm phase II study to evaluate the safety and efficacy of combination therapy of tailored-dose S-1 plus bevacizumab in patients with recurrent non-squamous NSCLC.
Method:
This was a prospective, multi-center, single-arm phase II study. Patients with non-squamous NSCLC who had experienced progression after cytotoxic chemotherapy were enrolled. Oral S-1 was administered on days 1–14 of a 21-day cycle, and bevacizumab (15 mg/kg) was given intravenously on day 1. Patients received S-1 adjusted on the basis of their creatinine clearance and body surface area. The primary endpoint was response rate (RR); secondary endpoints were progression-free survival (PFS), overall survival (OS), and safety.
Result:
We enrolled 30 patients. One patient had never received platinum-based therapy. Five patients had activating mutations of the epidermal growth factor receptor gene, of whom four had received tyrosine kinase inhibitors before this study. The RR was 6.7% (95% confidence interval (CI) 1.8–21.3%), and the disease control rate (DCR) was 80% (95% CI 62.7–90.5%). Median PFS was 4.8 months (95% CI 2.7–6.4 months], and median OS was 13.8 months (95% CI 8.4 months – not applicable). Patients did not experience any Grade 4 toxicity or treatment-related death. Grade 3 hematologic toxicity (anemia) occurred in one patient (3.3%). The main Grade 3 non-hematologic toxicities were anorexia (10%), infection (10%), and diarrhea (6.7%).
Conclusion:
The addition of bevacizumab to S-1 was tolerable, but not beneficial for patients with previously treated non-squamous NSCLC. We do not recommend further study of this regimen.
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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: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.03-008 - Phase I/II Study of Intermitted Erlotinib in Combination with Docetaxel in Patients with Recurrent NSCLC with Wild-Type EGFR: WJOG 4708L (ID 7556)
09:30 - 09:30 | Author(s): T. Kijima
- Abstract
Background:
Erlotinib (ERL) is modestly active to non-small cell lung cancer (NSCLC) with wild type epidermal growth factor receptor (EGFR). We hypothesized that an intermittent delivery of erlotinib and docetaxel (DOC) would increase efficacy.
Method:
This was a multi-center, single-arm phase I/II study in patients with wild type EGFR NSCLC who failed one prior chemotherapy. The phase I was designed a standard 3+3 dose escalation design to determine feasibility, the maximum tolerated dose (MTD) and phase II recommend dose (RD) of ERL on days 2 to 16, in combination with a fixed dose of 60mg/m[2] DOC on day 1. The phase II primary endpoint was objective response rate (ORR) by independent review committee. This study required 41 patients with expected ORR of 30% and threshold ORR of 10% (one-sided α= 0.025; β=0.1). The target number was 45 patients assuming the loss of follow-up cases. All eligible patients had ECOG performance status of 0/1 and adequate organ functions.
Result:
Between Mar 2009 and Dec 2010, 12 patients were enrolled in the phase I, and between May 2011 and Feb 2015, 46 patients in the phase II. Five patients were excluded from per protocol set, because of deviation of entry criteria. Planned dose escalation was completed without reaching a MTD. The RD was determined as 150 mg/dose of ERL. In the phase II, the ORR was 17.1% (95%CI, 7.2-32.1). The median progression free survival and median overall survival were 3.48 months (95%CI, 3.06-4.50) and 11.27 months (95%CI, 8.61-16.56), respectively. Gender, smoking status, or concomitant drugs which influence the ERL metabolism had no significant differences in ORR, or disease control rate. All 46 patients were evaluable for toxicity. The grade 3 non-hematological toxicities included 9 (19.6%) febrile neutropenia, 7 (15.2%) appetite loss, 3 (6.5%) oral mucositis and 3 (6.5%) infections. The grade 4 hematological toxicities were 31 (67.4%) neutropenia. Two treatment related deaths were observed; interstitial lung disease, and pleural infection.
Conclusion:
Intermittent dosing of ERL plus DOC is clinically feasible, but has no statistically significant improvement of ORR, in patients with recurrent NSCLC with wild type EGFR.
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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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P2.07-009 - Monitoring Nivolumab Binding as a Method to Clarify the Residual Therapeutic Effects in Previously Treated Lung Cancer Patients (ID 8098)
09:30 - 09:30 | Author(s): T. Kijima
- Abstract
Background:
Although the biological durability of Nivolumab, the PD-1 blocking antibody, was reported to continue longer than 12 weeks, the maximum duration of its efficacy, along with toxicity, after discontinuation and the correlation between residual binding and clinical events in cases of sequential therapeutic regimens remain unclear.
Method:
Peripheral blood, pleural effusion and bronchoalveolar lavage fluid were obtained from non-small cell lung cancer patients previously treated with Nivolumab. To evaluate the efficacy of the treatment, we developed a simple technique to identify Nivolumab binding status — complete binding, partial binding and no binding — in T cells from patient samples using flowcytometry, which can also be used to obtain T cell differentiation markers and transcriptome profiles, particularly in the Nivolumab bound T cell population. Based on this method, we tracked the binding status in T cells primarily from peripheral blood in patients who received a sequential therapeutic regimen after Nivolumab treatment.
Result:
While the decrease in frequency of Nivolumab binding after discontinuation was observed in all cases where long term monitoring was possible, Nivolumab binding in T cells from peripheral blood was detected until more than 20 weeks, though effective binding could have ceased before that time point. We found that the direct effects on Nivolumab binding via sequential treatment were limited. Finally, we observed in clinical cases that our monitoring technique was also helpful in understanding the cause of clinical events and its residual efficacy in patients who previously received Nivolumab.
Conclusion:
Monitoring of Nivolumab binding to T cells after discontinuation can be valuable when planning sequential therapeutic regimens in the following ways: estimating the potential residual efficacy, predicting the risk of immune-related adverse events and the time of relapse due to complete loss of efficacy, and investigating the changes in the immune profile in Nivolumab bound T cells.
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P2.09 - Mesothelioma (ID 710)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Mesothelioma
- Presentations: 1
- Moderators:
- Coordinates: 10/17/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P2.09-005a - Clinical Characteristics of Early Stage, Malignant Pleural Mesothelioma (ID 10043)
09:30 - 09:30 | Author(s): T. Kijima
- Abstract
Background:
While the mortality rate has markedly improved for primary lung cancer, a disease that used to be incredibly difficult to treat, the prognosis for malignant pleural mesothelioma (MPM) is as poor as ever, with a mean survival time (MST) after diagnosis of about 1 year. Therefore, it is thought that the most practical method of obtaining better survival times than those associated with currently available treatment options is diagnosing MPM at an earlier stage than is possible now. We performed a retrospective study to evaluate the clinical characteristics of early stage MPM.
Method:
The study included 83 patients with a definitive MPM diagnosis of International Mesothelioma Interest Group (IMIG) clinical stage T0-1a/1bN0M0. We selected 40 patients who did not exhibit significant fluorodeoxyglucose (FDG) accumulation (<2.5) in FDG-positron-emission tomography (PET) prior to starting treatment, and then retrospectively examined their clinical characteristics.
Result:
There were 4 women in this study, 5 patients with no history of asbestos exposure, 37 patients with epithelial histology, 3 patients with biphasic histology, and 3 patients with negative cytology. All patients had pleural effusion.
Conclusion:
Although this was a retrospective study, we found that among T0-1a/1bN0M0 and PET-negative MPM patients, positive cytology (class IV/V) and histology (biphasic) were factors associated with a poor prognosis.
