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Shunichi Sugawara
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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
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P1.01-08 - Randomized Phase II Trial of CBDCA+nab-PTX vs CDDP+GEM in Patients with Chemo-Naïve Squamous Cell Lung Cancer: NJLCG1302 (Now Available) (ID 971)
09:45 - 18:00 | Author(s): Shunichi Sugawara
- Abstract
Background
The subset analysis of CA031 trial showed a significant improvement of overall response rate (ORR) for carboplatin (CBDCA) plus weekly nab-PTX versus CBDCA plus PTX in patients (pts) with squamous cell histology (41% vs 24%). We conducted a phase II study comparing CBDCA plus weekly nab-PTX (CnP) to cisplatin plus gemcitabine (CG), one of the standard regimens in pts with squamous cell lung cancer (SCC).
Method
Chemo-naïve stage IIIB/IV or postoperative recurrent SCC pts were randomly assigned to receive either cisplatin (80 mg/m2) on day 1 plus gemcitabine (1000 mg/m2) on days 1, 8 every 3 weeks or CBDCA (area under the curve [AUC] 6 mg/ml/min) on day 1 plus nab-PTX (75 mg/m2) on days 1, 8, 15 every 3 weeks. The primary endpoint was ORR. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR) and toxicity. Assuming that an ORR of 40% in eligible pts indicates potential usefulness and ORR of 20% is the lower limit of interest, the estimated accrual was 32 pts in each arm. Allowing for dropouts, the accrual goal was determined to be 35 pts in each arm (alpha, 0.05; beta, 0.20).Thisstudy was planned to enroll 70 pts in total.
Result
Between June 2013 and October 2018, 71 pts were enrolled and assigned to CG arm (n=35) and CnP arm (n=36). The median follow-up time was 10.8months. At data cutoff (March 31, 2019), ORR was 43% (95% confidence interval [CI]: 27.3-58.5) in CG arm and 47% (95%CI: 31.7-62.7) in CnP arm. DCR was 77% in CG arm and 80% in CnP arm. Median PFS was 4.6 months in CG arm and 4.1months in CnP arm. Median OS was 15.2months in CG arm and 10.2months in CnP arm. Of the grade 3 or higher adverse events, anemia was more common in CnP arm (CG, 17% and CnP, 53%). There was one treatment-related death in CG arm and no treatment-related death in CnP arm.
Conclusion
In this study, CBDCA plus weekly nab-PTX was likely to be equivalent to cisplatin plus gemcitabine despite carboplatin-based regimen. CBDCA plus weekly nab-PTX could be a promising regimen for SCC.
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P1.16 - Treatment in the Real World - Support, Survivorship, Systems Research (ID 186)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 2
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.16-29 - Profiling Immune-Related Adverse Events (irAEs) in Patients with Anti-PD-1 for Advanced Non-Small Cell Lung Cancer (ID 416)
09:45 - 18:00 | Author(s): Shunichi Sugawara
- Abstract
Background
Immune-related adverse events (irAEs) are frequently observed during anti-programmed death-1 antibody therapy. We previously reported that patients with irAEs were associated with clinical efficacy. However, little is known about which irAEs are related with clinical efficacy in patients with non-small cell lung cancer (NSCLC). This study aimed to evaluate the correlations between different irAEs and treatment response.
Method
Patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at our hospital (n=154) from January 2016 to April 2018 were included in this study. Subjects were categorized into the irAE-incident group (with irAEs group) or non-irAE-incident group (without irAEs group), specific for each irAE. We evaluated the objective response rate (ORR), time to treatment failure (TTF), progression-free survival (PFS), and overall survival (OS) in each group.
Result
The categorization of irAEs identified 51 cases of skin reactions (31%), 16 of infusion reactions (10%), 19 of pneumonitis (12%), 21 of thyroid dysfunction (14%), and 10 of hepatitis (6%). In the with/without skin reaction groups, the ORRs were 57% (29 cases)/19% (20 cases) (p<.001), median TTFs (months) were 8.7/2.8 (p<.001), median PFSs were 12.9/3.4 months (p<.001), and median OSs were NR/11.4 months (p<.001), respectively. In the with/without infusion reaction groups, the ORRs were 56% (9 cases)/29% (40 cases) (p=.05), median TTFs were 7.6/3.7 months (p=.11), median PFSs were 11.1/4.1 months (p=.045), and median OSs were NR/14.8 months (p<.001), respectively. In the with/without pneumonitis groups, the ORRs were 63% (12 cases)/27% (37 cases) (p=.004), median TTFs were 4.4/3.7 months (p=.44), median PFSs were 18.9/4.1 months (p=.02), and median OSs were NR/14.8 months (p=.09), respectively. In the with/without thyroid dysfunction groups, the ORRs were 52% (11 cases)/29% (38 cases) (p=.08), median TTFs were 7.4/3.7 months (p=.63), median PFSs were 8.7/4.2 months (p=0.22), and median OSs were 11.8/15.9 months (p=.84), respectively. In the with/without hepatitis groups, the ORRs were 40% (4 cases)/31% (45 cases) (p=.82), median TTFs were 2.7/4.1 months (p=.42), median PFSs were 6.4/4.20 months (p=.70), and median OSs were NR/15.6 months (p=.43). The PFS was significantly longer in patients with skin reactions, infusion reactions, and pneumonitis than that in those without, whereas the OS was significantly longer in patients with skin and infusion reactions than that in those without.
Conclusion
The development of skin and infusion reactions during nivolumab or pembrolizumab monotherapy for NSCLC might be strongly associated with improved clinical efficacy, and clinical benefits should be validated through large-scale prospective analysis.
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P1.16-34 - Association Between Skin Reactions and Clinical Benefit in Patients Treated with Anti-PD-1 Treatment for Advanced Non-Small Cell Lung Cancer (Now Available) (ID 420)
09:45 - 18:00 | Author(s): Shunichi Sugawara
- Abstract
Background
Anti-Programmed death-1 antibody is now standard therapy for advanced non-small cell lung cancer (NSCLC). However, immune-related adverse events (irAEs) including skin reactions are frequently observed. In melanoma, skin reactions and clinical efficacy are reportedly associated. However, little is known about this association in NSCLC. In addition, predictive markers of irAEs remain unknown. This study aimed to evaluate whether skin reactions correlate with clinical efficacy and identify potential clinical biomarkers that may meaningfully and conveniently predict skin reactions following treatment.
Method
We retrospectively surveyed patients with advanced NSCLC who received nivolumab or pembrolizumab monotherapy at Sendai Kousei Hospital (n=155) between January 2016 and April 2018. The patients were categorized into two groups based on the development of skin reactions during treatment. Treatment efficacy was evaluated in each group, and predictive markers of skin reactions were determined. Furthermore, we also conducted 6-week landmark analysis to assess the association between early skin reactions and clinical benefit.
Result
In the cohort of 155 patients (median [range] age, 68 [31-88] years; 117 men [75%], 38 women [25%]), skin reactions were observed in 52 (33%) patients. The median duration of onset of skin reactions was 6.4 weeks. The overall response rate (ORR) was significantly higher in patients with skin reactions than that in those without (57% vs. 19%; P<.001). The median progression free survivals (PFSs) were 12.9(95% confidence interval (CI), 8.5–not reached(NR)) and 3.4 (95% CI, 2.5-4.1) (P<.001) months, whereas the median overall survivals (OS) were NR (95% CI, 17.4-NR) and 11.4 months (95% CI, 8.8-15.6) (P<.001) in patients with and without skin reactions, respectively. In 6-week landmark analysis, the ORR was significantly higher in patients with skin reactions than that in those without (28 of 49 patients [57.1%] vs. 20 of 106 patients [18.9%]; P <.001), and the development of skin reactions was significantly associated with increased PFS (with skin reactions median PFS = 10.3 months, 95% CI, 5.6-NR ; without, median PFS = 4.2 months, 95% CI, 3.6-5.9; P=.045). Furthermore, multivariate analysis revealed that pre-existing rheumatoid factor (RF) was an independent predictor of skin reactions (odds ratio, 3.39; 95% CI, 1.56–7.33; P=.003).
Conclusion
The development of skin reactions was associated with clinical benefit in patients treated with nivolumab and pembrolizumab for NSCLC. Pre-existing RF also served as an independent predictor of skin reactions. Further studies with large patient samples are necessary to validate these findings.
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P2.04 - Immuno-oncology (ID 167)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.04-65 - Peptide-Based Cancer Vaccine Shortened the Overall Survival of a Large Portion, but Not All, of Advanced Cancer Patients (ID 1854)
10:15 - 18:15 | Author(s): Shunichi Sugawara
- Abstract
Background
We have been promoting clinical trials of peptide-based cancer vaccination for various cancers, mainly at Kurume University School of Medicine.
Method
Objective: To determine biomarkers predictive of overall survival (OS) in advanced cancer patients treated with a peptide-based cancer vaccine.
Patients: The samples from two randomized, double-blind, placebo-controlled, phase III trials of personalized peptide vaccine (PPV) for advanced prostate cancer patients (n=306) and recurrent glioblastoma (n=88) patients, those from one single arm phase II trial of PPV for various types of advanced cancer patients (n=2588), and those from one randomized placebo-controlled non-personalized phase II trial (n=51) for advanced prostate cancer patients were provided for this retrospective biomarker study.
Result
No significant differences in clinical benefit (overall survival, OS) were found between the patients receiving PPV and those receiving placebo in each of the two randomized, double-blind, placebo-controlled, phase III trials. The neutrophil or lymphocyte proportion in advanced prostate cancer patients prior to study entry was a biomarker discriminating the PPV patients (70%) who showed significantly shorter OS relative to placebo patients from the remaining PPV patients who showed significantly longer OS relative to placebo patients. The C-C motif chemokine 2 (CCL2) level prior to the study entry in recurrent glioblastoma patients was the other biomarker discriminating the PPV patients (40%) who showed significantly shorter OS relative to placebo patients from the remaining PPV patients who showed significantly longer OS relative to placebo patients.
The neutrophil or lymphocyte proportion prior to the phase II study entry (n=2588) was also a biomarker discriminating the PPV patients (60%) with significantly shorter OS from the remaining PPV patients entered in the single arm phase II study in all the advanced cancer patients other than gastric cancer or glioblastoma patients. Notably, the median OS for the 250 of 399 lung cancer patients (62 %) who met either or both the cutoffs of neutrophils ³64% and lymphocytes <26% was significantly shorter than that of the remaining 149 patients (38%) (9.5 month,95% confidence interval: 7.6-11.9 vs 20.0 month,13.0-25.3, p<0.001). The CCL2 level, however, prior to the study entry was not a biomarker in these lung cancer patients receiving PPV. This biomarker was also predictive of OS in a randomized placebo-controlled non-personalized phase II trial of peptide-based vaccine.
Conclusion
Peptide-based cancer vaccine shortened the OS of a large portion, but not all, of advanced cancer patients with various types of cancer. Prospective clinical studies of peptide-based cancer vaccines using the newly defined prognostic markers may be warranted.
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P2.14 - Targeted Therapy (ID 183)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.14-52 - The Results from Plasma EGFR Mutation Analysis in NEJ026 Study (ID 602)
10:15 - 18:15 | Author(s): Shunichi Sugawara
- Abstract
Background
EGFR mutation analysis of plasma circulating tumor DNA (ctDNA) has been reported to be useful to detect resistant mutations and to predict the efficacy of treatment. In NEJ026 study, we demonstrated the PFS of erlotinib plus bevacizumab (BE) treatment was significantly superior to the erlotinib alone (E) in NSCLC patients harboring EGFR mutation. Evaluation of plasma EGFR mutations included in NEJ026 study as preplanned analysis.
Method
At the time points of pretreated (P0), 6 weeks after study treatment started (P1), and confirmed progressive disease (P2), the plasma samples were collected from the patients enrolled to NEJ026 study. The number of enrolled patients were 112 in BE and 114 in E. Plasma ctDNA analysis for detection of the activating EGFR mutation and T790M mutation were performed by modified PNA-LNA PCR clamp method.
Result
The total numbers of collected plasma samples in BE and E were 108 (96.4%) and 107 (95.5%) at P0, 95 (84.8%) and 97 (86.6%) at P1, and 42 (37.5%) and 53 (47.3%) at P2, respectively. In eligible patients having EGFR activating mutation detected by cytohistological specimens, detection rate of plasma EGFR mutation at P0 was 68% (147/215). The detection ratio of T790M mutation at P2 were similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. By detection pattern of activating EGFR mutation, PFS was evaluated among three groups: type A (P0 (-),P1 (-)), type B (P0 (+), P1(-)), and type C (P0 (+), P1(+)). Type A achieved the best response to both TKI [Type A BE: 18.1 M (n = 32, 95% CI, 11.5 to upper limit not reached(NR)), E: 16.7 M (n = 26, 95% CI, 11.2 to NR )]. Type B also had better PFS to TKI and BE is more favorable effect than E compared to other types [type B BE: 15.5 M (n = 48, 95% CI, 12.4 to 23.3), E: 11.1 M (n = 57, 95% CI, 8.5 to 13.7)]. Type C showed worse response to both treatment [type C BE: 6.0M. (n = 12, 95% CI 2.6 to NR), E: 4.3 M (n = 10, 95% CI, 2.8 to 20.2)]. BE had better PFS in all types.
Conclusion
Frequency of T790M in P2 was similar among BE and E. When patients still had detectable activating EGFR mutation in plasma ctDNA after treatment for 6 weeks, you should consider that they might have poor response to both BE and E.
