Virtual Library
Start Your Search
Takaaki Tokito
Author of
-
+
MA13 - Going Back to the Roots! (ID 139)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:Maurice Perol, Kaoru Kubota
- Coordinates: 9/09/2019, 14:00 - 15:30, Vancouver (2003)
-
+
MA13.07 - Phase I/II Study of Carboplatin Plus Weekly Nab-Paclitaxel in Aged ≥75 Patients with Squamous-Cell Lung Cancer: TORG1322 (Now Available) (ID 1369)
14:00 - 15:30 | Author(s): Takaaki Tokito
- Abstract
- Presentation
Background
Combination chemotherapy of carboplatin (CBDCA) plus weekly nab-paclitaxel (nab-PTX) showed a favorable efficacy for elderly (70 year or older) patients with squamous non-small cell lung cancer (Sq-NSCLC) in a subgroup analysis of the CA031 study. We conducted a phase I/II study of CBDCA plus nab-PTX in chemo-naïve elderly patients with advanced Sq-NSCLC.
Method
Patients aged ≥75 years with untreated, measurable lesion, advanced Sq-NSCLC, performance status (PS) 0-1, and adequate organ function were eligible. In a phase I study, doses of carboplatin at an area under the curve (AUC) of 5 or 6 mg/mL min on day 1 (levels 1 and 2, respectively) were administered along with weekly nab-PTX (100 mg/m2) on days 1, 8, and 15 every 4 weeks up to 6 cycles using a modified 3 + 3 design. The primary endpoint for the phase II study was the 6-month progression-free survival (6m PFS) rate and hypothesis required 36 patients to be enrolled with expecting and threshold values for the primary endpoints of 40% and 25% (one-sided alpha = 0.05; beta = 0.2).
Result
A total of 46 patients were enrolled in this study. The median age was 78 (range 75-85 years); male (n = 41); PS 0/1, (n = 15/31). Ten patients were enrolled in the phase I part. At dose level 1, 2/7 patients showed dose-limiting toxicities (DLTs) of grade 3 diarrhea and febrile neutropenia, and at dose level 2, 1/3 patient showed DLT of grade 3 anorexia. The recommended dose was determined to be level 2. Additional 36 patients were enrolled, and a total of 39 patients were evaluated in the phase II study. The median number of cycles was 4 (range 1-6), and the median follow-up time was 17.5 months (range 5.6-28.9). The 6m PFS rate was 59% (90% CI, 44.8-71.4), and the primary endpoint was met. The median overall survival time was 23.5 months (95% CI, 11.6-35.4), and the median PFS was 6.8 months (95% CI, 5.4-9.1). The response rate was 54% and disease control rate was 92%. Nineteen patients (49%) received post-study treatment and 14 out of 19 patients (74%) received immunotherapy. Common toxicities of grade 3 or 4 were neutropenia (61.5%), anemia (46.2%), thrombocytopenia (17.9%), and febrile neutropenia (15.4%). There was no treatment-related death.
Conclusion
Combination chemotherapy of CBDCA plus weekly nab-PTX had a promising efficacy and acceptable toxicities in elderly (aged ≥75) patients with advanced Sq-NSCLC. Clinical trial information: UMIN000011216.
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.
-
+
P1.01 - Advanced NSCLC (ID 158)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.01-15 - Multicenter, Single-Arm Phase II Study of Nab-Paclitaxel/Carboplatin in Untreated PS2 Patients with Advanced NSCLC: TORG1426 (Now Available) (ID 519)
09:45 - 18:00 | Author(s): Takaaki Tokito
- Abstract
Background
Performance Status (PS) has been shown to predict survival in patients with advanced non-small cell lung cancer (NSCLC). To date, PS2 patients have been underrepresented in clinical trials due to concerns about tolerability. Consequently, no standard of care exists for these patients. In CA031 trial, nab-paclitaxel/carboplatin (nab-PTX/CBDCA) demonstrated significantly higher response rate (RR) compared with PTX/CBDCA in PS0-1 patients with advanced NSCLC. Furthermore, in elderly subgroup, nab-PTX/CBDCA tended to show superior progression-free survival (PFS) and overall survival (OS) based on better tolerability compared with PTX/CBDCA. Therefore, this phase II trial was designed to characterize the efficacy, safety, and tolerability of nab-PTX/CBDCA in untreated PS2 patients with advanced NSCLC.
Method
Chemotherapy-naive PS2 patients with stage IIIB/IV NSCLC were treated with nab-PTX (70 mg/m2 on day1, 8, and15, q4w) and CBDCA (AUC 5 on day1, q4w) up to 6 cycles if they did not have uncontrolled brain metastasis or pleural effusion. The primary endpoint was PFS rate at 6 months. Its achievement of more than 50% was considered worthy of further development of this regimen, whereas that of less than 30% was considered insufficient for further investigation. The estimated power was 80% with type I error of 0.05, resulting in 35 patients needed. Concurrently, Symptom Score and Charlson Comorbidity Index (CCI) were evaluated.
Result
This trial was terminated due to slow accrual. Between September 2015 and August 2018, 17 patients (median age, 68 years [range, 50-73]) were enrolled and received a median of 3 cycles. The reasons for PS2 were tumor progression (71%), comorbidities (12%), or both (17%). The PFS rate at 6 months was 20.8% (95% confidence interval, 0%-41.6%). The median PFS, OS, RR, and disease control rate (DCR) were 3.0 months, 9.5 months, 17.4%, and 70.6%, respectively. Grade 3-5 adverse events (AE) included fatigue (24%), lung infection (24%, including 6% of grade 5), neutropenia (18%), and anemia (18%), resulting in trial withdrawal rate of 24%. The median PFSs of 11 patients with and 6 patients without 2nd line chemotherapy were 5 months and 1.7 months, respectively (p = 0.009). Symptom Score was improved by chemotherapy (p = 0.004), whereas comparison between lower and higher CCI values demonstrated no difference regarding chemotherapy cycles administered (p = 0.5) and regarding chemotherapy efficacy (p = 0.268).
Conclusion
Nab-PTX/CBDCA did not meet its primary endpoint, but could be a feasible treatment option for untreated PS2 patients with advanced NSCLC. Clinical trial information: UMIN000019458
-
+
P1.14 - Targeted Therapy (ID 182)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
-
+
P1.14-30 - Phase I Study of Afatinib Plus Bevacizumab in Patients with Advanced Non-Small Cell Lung Cancer Harboring EGFR Mutations (ID 1580)
09:45 - 18:00 | Presenting Author(s): Takaaki Tokito
- Abstract
Background
Afatinib, a second-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is one of the standard therapies for patients with advanced non-small cell lung cancer (NSCLC) harboring EGFR mutations. The first-generation EGFR-TKIs in combination with bevacizumab have been reported to improve progression-free survival (PFS). However, data on afatinib plus bevacizumab are limited.
Method
In this phase I study, we examined the safety and the efficacy of afatinib plus bevacizumab in patients with advanced non-squamous NSCLC harboring EGFR mutations. This study comprised two cohorts. In the dose-finding cohort, eligible patients received afatinib 20, 30, or 40 mg/day (days 1–21) plus bevacizumab 15 mg/kg (day 1) in 21-day cycles. This cohort was designed and conducted in a 3 + 3 manner. In the expansion cohort, the patients were treated with the recommended dose (RD) based on the findings in the dose-finding cohort, and we evaluated the preliminary efficacy of this combination therapy. The serum trough concentration of afatinib was assessed at the steady state.
Result
Sixteen patients were enrolled in this study (5 patients in the dose-finding cohort and 11 patients in the expansion cohort). No dose-limiting toxicities (DLTs) occurred with afatinib 30 mg/day. With afatinib 40 mg/day, 2 out of 2 patients had DLTs (grade 3 diarrhea) in cycle 1. From these results, afatinib 30 mg/day plus bevacizumab 15 mg/kg was decided as the RD. Additionally, 11 patients in the expansion cohort were treated with RD. Common treatment-emergent adverse events (AEs) with the RD were diarrhea (79%), rash (71%), perionychia (64%), and stomatitis (50%). Grade 3 AEs with the RD were diarrhea (7%), perionychia (7%), and hypertension (7%). There were no grade 4/5 AEs and interstitial lung disease. The response rates and median PFS were 56% and 16.8 months in EGFR-TKI naïve patients, and 0% and 4.9 months in patients pretreated with EGFR-TKIs. The median serum concentration at the steady state was 13.7 ng/mL (range: 8.1–38.1 ng/mL) in the patients treated with the RD. Rebiopsy was conducted in eight patients after disease progression with afatinib plus bevacizumab, and three patients acquired an exon 20 T790M mutation.
Conclusion
Afatinib 30 mg/day plus bevacizumab 15 mg/kg was well tolerated. Large-scale studies are warranted to evaluate the efficacy of this combination therapy.
-
+
P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
-
+
P2.04-01 - Changes of BCR Repertoire Are Predictive Biomarker for the Efficacy of Immune Checkpoint Inhibitor in NSCLC (ID 1688)
10:15 - 18:15 | Author(s): Takaaki Tokito
- Abstract
Background
Clonal diversity of T cell receptor (TCR) and/or B cell receptor (BCR) repertoires might play a major role in antitumor immunity in cancer patients. Assessment of TCR and BCR repertoires might enable us to predict the efficacy of immune checkpoint inhibitors (ICI).
Method
The study population comprised 30 patients with non-small-cell lung cancer (NSCLC), who started treatment with nivolumab (3mg/kg, every two weeks) or pembrolizumab (200mg, every three weeks) between February 2016 and August 2017. Patient blood samples were collected before and four to six weeks after the initiation of treatment. TCR and BCR chain sequences were determined by using the unbiased gene amplification method with Adaptor-Ligation PCR. The diversity of TCR and BCR repertoires was evaluated with inverse Shannon-Weaver index (iSWI).
Result
We compared the iSWI between before and after treatment. The fold changes of iSWI in BCR repertoire after treatment in patients with PR were significantly higher than those with SD or PD. In contrast, the fold changes of iSWI in TCR repertoire after treatment were not associated with tumor responses. When the cut-off value of fold change of iSWI in BCR repertoire after treatment was determined as 0.85, 25 (83%) and 5 (17%) patients were considered as high and low fold change group, respectively. Progression free survival in the high fold change group was significantly longer compared with that in the low fold change group (182 vs 49 days; 95% confidence interval (CI);99-N.R. vs 31-168 days, respectively; P=0.01).
Conclusion
Our findings suggest that reduced repertoire diversity in BCR, but not in TCR, might be associated with better clinical outcomes in advanced NSCLC patients treated with ICI. Assessment of the changes of BCR repertoire after treatment might be useful for predicting the efficacy of ICI. The present results require confirmation in a large-scale prospective study.
-
+
P2.04-85 - Clinical Significance of the PD-L2 Expression in Patients with NSCLC Receiving Anti-PD-1 Inhibitors (ID 1611)
10:15 - 18:15 | Author(s): Takaaki Tokito
- Abstract
Background
The programmed cell death 1 (PD-1) receptor–ligand interaction is a major pathway often hijacked by tumors to suppress immune control. Programmed cell death-ligand 1 (PD-L1), a ligand of PD-1, can potentially predict the response to anti-PD-1/PD-L1 inhibitors in patients with non-small cell lung cancer (NSCLC); however, the role of PD-L2, another ligand of PD-1, remains unclear in patients receiving anti-PD-1 inhibitors. This retrospective study aims to determine the significance of the PD-L2 expression in anti-PD-1 inhibitors–treated patients with NSCLC.
Method
We enrolled 82 patients with advanced or recurrent NSCLC who received anti-PD-1 inhibitors. The PD-L2 expression was assessed by immunohistochemical analysis staining with an antibody of PD-L2 (1:200, clone 176611), and cases with >1% tumor staining of PD-L2 were considered positive. Furthermore, we analyzed correlations between PD-L2 expression and patients’ characteristics, efficacy, and immune-related adverse events (irAEs) of anti-PD-1 inhibitors.
Result
In this study, 59 (72.0%) and 56 (68.3) patients with NSCLC exhibited positive tumor PD-L2 and PD-L1 staining, respectively. Overall, 39 irAEs developed in 36 patients. The PD-L2 expression markedly correlated with the development of irAEs; however, we observed no correlation between PD-L2 expression and the efficacy of anti-PD-1 inhibitors. Other factors, including the PD-L1 expression, age, sex, smoking status, histology, did not correlate with the development of irAEs.
Conclusion
This study suggests that the PD-L2 expression could be accountable for the development of irAEs in anti-PD-1 inhibitors–treated patients with NSCLC.
