Virtual Library
Start Your Search
M. Takenoyama
Author of
-
+
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
-
+
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): M. Takenoyama
- 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.
Only Members that have purchased this event or have registered via an access code will be able to view this content. To view this presentation, please login, select "Add to Cart" and proceed to checkout. If you would like to become a member of IASLC, please click here.
-
+
P1.08 - Locally Advanced NSCLC (ID 694)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Locally Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/16/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
-
+
P1.08-006 - Phase I/II Study of Carboplatin, nab-paclitaxel, and Concurrent Radiation Therapy for Patients with Locally Advanced NSCLC. (ID 8356)
09:30 - 09:30 | Author(s): M. Takenoyama
- Abstract
Background:
A regimen of weekly paclitaxel plus carboplatin (CBDCA) with concurrent thoracic radiotherapy is recognized as standard for patients with unresectable stage III lung cancer. Nanoparticle albumin-bound paclitaxel (nab-PTX) is a cremophor-free formulation of paclitaxel to increase solubility and intratumor drug delivery and is effective for patients with advanced NSCLC. The purpose of this study is to determine recommended dose and investigate the efficacy and safety profile of a regimen of nab-PTX plus CBDCA with concurrent thoracic radiotherapy for patients with unresectable non-small cell lung cancer (NSCLC).
Method:
Patients with unresectable stage IIIA or IIIB NSCLC, good performance status, age between 20 and 74 years, and adequate organ function, a relative volume of normal lung receiving a dose of ≥ 20 Gy (V20) ≤35% were eligible. In a phase I study (standard 3+3 design), weekly nab-PTX plus CBDCA was administered intraveneously for six weeks. Doses of each drug were planned as follows: level 1, 40/2; level 2, 50/2 (nab-PTX [mg/m[2]] / CBDCA [area under the plasma concentration time curve (AUC) mg/ml/min]). Concurrent thoracic radiotherapy was administered in 2 Gy fractions to a total dose of 60 Gy. Dose-limiting toxicity (DLT) was observed during concurrent chemotherapy and thoracic radiation and up to 28 days following the end of radiotherapy. After the evaluation of DLT, patients received an additional two cycles of consolidation chemotherapy that consisted of 3-week cycles of nab-PTX (100 mg/m[2] on Days 1, 8 and 15) plus CBDCA (AUC 6 mg/ml/min on Day 1). In a phase II study, we planned to enroll 50 patients treated with recommended dose.
Result:
In a Phase I study, 11 patients were enrolled and received treatment per protocol, with 9 evaluable for efficacy and toxicity. At nab-PTX dose level 1 (40mg/m[2]), none of 3 patients experienced DLT. At nab-PTX dose level 2 (50mg/m[2]), 1 of 6 patients experienced DLT: grade 3 leukopenia requiring a second consecutive skip in the administration of weekly nab-PTX plus CBDCA. The recommended doses (RDs) for the phase II study were nab-paclitaxel 50 mg/m[2] and CBDCA (AUC=2). From October 2015 to November 2016, a total of 52 patients were entered in the phase II portion ( median age, 66 years; age range, 48–74 years; male/female 44/8) .
Conclusion:
Concurrent chemoradiotherapy with nab-PTX 50 mg/m[2] and CBDCA AUC 2 was the recommended dose. We will report the latest efficacy and safety profile of the present therapy. Trial registration: UMIN000012719.
-
+
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)
-
+
P2.09-005 - The C-reactive Protein/Albumin Ratio is a Novel Significant Prognostic Factor in Patients with Malignant Pleural Mesothelioma (ID 7375)
09:30 - 09:30 | Author(s): M. Takenoyama
- Abstract
Background:
Malignant pleural mesothelioma (MPM) is a devastating neoplasm. However, some patients show a good response to chemotherapy or multidisciplinary therapy. It is therefore important to investigate the factors that can be used to select patients who will benefit from such treatment. The C-reactive protein/albumin ratio (CAR) has been used to predict the prognosis in other diseases. The aim of this study was to elucidate the prognostic utility of the CAR in MPM patients.
Method:
The data of 83 patients, who were treated with surgery, chemotherapy, or multidisciplinary therapy at National Kyushu Cancer Center between 1995 and 2015, were analyzed in the present study. The CAR was calculated as C-reactive protein value divided by albumin value using the results of blood examination just prior to starting the treatments. A cut-off value of CAR was set to 0.58 according to the receiver operating characteristics (ROC) curve for 1-year-survival.
Result:
Thirty of the 83 (36.1%) patients were classified into the high CAR group. Twenty-seven (32.5%) and 56 (67.5%) patients underwent surgery and only chemotherapy, respectively. The ROC curve showed that the CAR had good diagnostic ability with 78.9% sensitivity and 68.0% specificity (AUC=0.761). A high CAR group was significantly correlated with advanced clinical stage (III/IV) (p=0.002) and chemotherapy alone (p=0.005). The high CAR group had significantly poorer overall survival (OS) (p<0.001) and disease or progression free survival (DFS/PFS) (p<0.001). The clinical stage and the CAR were independent predictive factors for the OS (I/II and III/IV, p=0.008; ≤0.58 and >0.58, p=0.034, respectively). The clinical stage and the CAR were also independent predictive factors for the DFS/PFS (I/II and III/IV, p=0.031; ≤0.58 and >0.58, p=0.019, respectively). In the subgroup analysis of the patients who underwent only chemotherapy, the high CAR group showed significantly poorer OS and DFS/PFS compared with the low CAR group (p=0.002 and p<0.001, respectively). However, the difference in OS and DFS/PFS of the patients who underwent surgery was not apparent between the high and low CAR groups (p=0.061 and p=0.187, respectively).
Conclusion:
The CAR was an independent predictor of a poor prognosis in the MPM patients. The high CAR group showed a significantly poorer prognosis in patients with MPM treated by only chemotherapy. This score provides useful information for selecting patients who will benefit from treatment, especially chemotherapy. These findings should be validated in further prospective studies.
