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Junji Uchino
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EP1.14 - Targeted Therapy (ID 204)
- Event: WCLC 2019
- Type: E-Poster Viewing in the Exhibit Hall
- Track: Targeted Therapy
- Presentations: 1
- Now Available
- Moderators:
- Coordinates: 9/08/2019, 08:00 - 18:00, Exhibit Hall
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EP1.14-05 - Clinical Characteristics of Osimertinib Responder in Non-Small Cell Lung Cancer Patients with EGFR-T790M Mutation (Now Available) (ID 207)
08:00 - 18:00 | Author(s): Junji Uchino
- Abstract
Background
Osimertinib is a mutant-selective EGFR inhibitor that is effective against non-small cell lung cancer (NSCLC) patients with the EGFR-T790M mutation, who are resistant to EGFR-tyrosine kinase inhibitors (EGFR-TKIs). However, the factors affecting response to osimertinib treatment are unknown.
Method
In this retrospective study, 27 NSCLC patients with the EGFR-T790M mutation were enrolled at 5 institutions in Japan.
Result
Among several parameters tested, the progression-free survival (PFS) associated with the initial EGFR-TKIs was positively correlated with the PFS after osimertinib treatment (p = 0.021). The median PFS following osimertinib treatment and the overall survival (OS) were longer in patients who responded to osimertinib than in those who did not (17.7 months versus 3.5 months, p = 0.009 and 24.2 months versus 13.5 months, p = 0.021, respectively). A multivariate analysis demonstrated that the PFS with initial EGFR-TKIs was significantly related to the PFS with osimertinib treatment (p = 0.035), whereas osimertinib response was significantly related to the PFS and OS with osimertinib treatment (p = 0.016 and p = 0.006, respectively).
Conclusion
Our retrospective observations indicate that PFS following the initial EGFR-TKI treatment and the response rate to osimertinib might be promising predictors for effective osimertinib treatment in NSCLC patients with the EGFR-T790M mutation.
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P1.04 - Immuno-oncology (ID 164)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Immuno-oncology
- Presentations: 2
- Moderators:
- Coordinates: 9/08/2019, 09:45 - 18:00, Exhibit Hall
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P1.04-34 - Efficacy and Safety of First-Line Pembrolizumab Monotherapy in Elderly Patients (Aged ≥ 75 years) with Non-Small Cell Lung Cancer (ID 265)
09:45 - 18:00 | Author(s): Junji Uchino
- Abstract
Background
Pembrolizumab is effective as first-line treatment for advanced non-small cell lung cancer (NSCLC) patients expressing high programmed death-ligand 1 (PD-L1). However, it is unclear whether the efficacy of first-line pembrolizumab treatment in elderly patients (aged ≥75 years) is similar to that in non-elderly patients expressing high PD-L1. Therefore, we aimed to investigate the efficacy and safety of first-line pembrolizumab monotherapy in elderly patients with NSCLC expressing high PD-L1.
Method
Between February 2017 and February 2018, 128 patients (comprising 47 elderly) with advanced NSCLC expressing high PD-L1 received first-line pembrolizumab monotherapy at 10 Japanese institutions. Baseline characteristics, efficacy of pembrolizumab treatment, and adverse events were recorded.
Result
Overall, 47 patients (40 men and 7 women) (median age, 79 [range, 75–88] years) were included in our analysis. In these patients who received first-line pembrolizumab monotherapy, the overall response, disease control rates, median progression-free survival (PFS), and overall survival (OS) were 53.1%, 74.4%, 7.0 months, and not reached, respectively. Common adverse events included anorexia, fatigue, skin rash, and hypothyroidism. Two treatment-related deaths due to pneumonitis and infection were noted. First-line pembrolizumab monotherapy with non-progressive disease (PD) was associated with better PFS. Pembrolizumab monotherapy with good performance status and non-PD was also linked to better OS.
Conclusion
First-line pembrolizumab monotherapy among elderly patients with NSCLC expressing high PD-L1 was effective and safe and showed outcomes equivalent to those in non-elderly patients. First-line pembrolizumab monotherapy without PD, and with good performance status and non-PD, might be associated with better PFS and OS, respectively.
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P1.04-40 - Serum Perforin Levels During the First Cycle of Anti-PD-1 Antibody Therapies in Non-Small Cell Lung Cancer (ID 1662)
09:45 - 18:00 | Author(s): Junji Uchino
- Abstract
Background
Blockade of PD-1 pathways by anti-PD-1 antibodies restore the function of exhausted T cells and release perforin and granzyme B which induce cytotoxic activity against tumor cells. We examined serum perforin and granzyme B as biomarkers of response to nivolumab and pembrolizumab in non-small cell lung cancer (NSCLC) patients.
Method
Advanced NSCLC patients treated with nivolumab or pembrolizumab were studied. Serum were collected on days 1, 2, 8 and 15 for nivolumab and on days 1, 2, 8, 15 and 22 for pembrolizumab. Concentration of perforin and granzyme B was determined by enzyme-linked immunosorbent assay (ELISA). Best objective response was evaluated by Evaluation Criteria in Solid Tumors (RECIST) 1.1.
Result
Sera from 40 patients with nivolumab and 26 patients with pembrolizumab were analyzed. Optimal cutoff levels for baseline concentration of perforin (day 1) were determined by efficacy. The calculated optimal cutoff levels were 5450.46 pg/ml with nivolumab (area under the receiver-operating-characteristic curve [AUC], 0.703) and 6631.16 pg/ml with pembrolizumab (AUC, 0.806). With nivolumab, median progression-free survival (PFS) was 6.8 months (95% confidence interval [CI], 2.8 to 3.7) in high concentration group (85%) versus 0.7 months (95% CI, 0.13 to not reached) in low concentration group (15%; hazard ratio [HR] for disease progression or death, 0.24; 95% CI, 0.09 to 0.68, p=0.007). Median overall survival (OS) was 14.9 months (95% CI, 10.2 to not reached) in high concentration group versus 1.8 months (95% CI, 0.13 to not reached) in low concentration group (HR for death, 0.19, 95% CI, 0.05 to 0.78, p=0.022). With pembrolizumab, median PFS was 6.7 months (95% CI, 3.5 to not reached) in high concentration group (73%) versus 0.7 months (95% CI, 0.37 to 5.7) in low concentration group (26%; HR for disease progression or death, 0.31; 95% CI, 0.11 to 0.89; p=0.03). Median OS was not reached (95% CI, 7.9 to not reached) in high concentration group versus 2.1 months (95% CI, 0.57 to not reached) in low concentration group (HR for death, 0.2; 95% CI, 0.05 to 0.77; p=0.018). Ratios of sequential perforin levels to baseline levels were analyzed, however, their AUC were not high enough, considered as low predictive power. Serum granzyme B was difficult to measure by ELISA.
Conclusion
With anti-PD-1 antibody therapies, in patients with advanced NSCLC, higher baseline serum perforin levels before treatment were associated with significantly longer progression-free and overall survival.
