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Y. Koh
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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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P2.03-045 - Updated Results of Phase II, Liquid Biopsy Study in EGFR Mutated NSCLC Patients Treated with Afatinib (WJOG 8114LTR) (ID 9715)
09:30 - 09:30 | Author(s): Y. Koh
- Abstract
Background:
Liquid biopsy has been approved as an optional method to detect clinically relevant EGFR mutations in NSCLC. WJOG8114LTR is a prospective, multi-institutional study of liquid biopsy in EGFR mutated NSCLC patients. Previously, we reported that complete molecular response at 4 weeks could be an early surrogate marker of durable efficacy. Here, we report updated results.
Method:
Chemotherapy naïve, advanced NSCLC patients with EGFR-sensitizing mutation received afatinib monotherapy (40 mg/body) until progressive disease (PD) or unacceptable toxicity. Plasma DNA was obtained from patients at baseline, weeks 2, 4, 8, 12, 24, 48, and at PD. Three types of clinically relevant EGFR mutations (exon 19 deletion, exon 20 T790M and exon 21 L858R) will be analyzed using plasma DNA with multiplexed, pico-droplet digital PCR assay (RainDrop® system, RainDance Technologies, Billerica, MA). Complete molecular response (CMR) was defined as mutant allele event/frequency of exon 19 deletion or exon 21 L858R below the cutoff for the positivity by digital PCR in plasma. This study was registered at UMIN (ID: 000015847).
Result:
Fifty-seven patients were registered in the study. Efficacy of afatinib was comparable to previous reports (overall response rate: 78.6%, and median progression-free survival (mPFS): 14.2 months). At baseline, 62.5% of patients (35/56) were positive for EGFR mutation in plasma. Among those, CMR rate at 2, 4, 8, 12, 24 weeks was 60.6%, 87.5%, 93.8%, 87.1%, and 83.3%, respectively. About 40% of patients who achieved CMR at any time point maintain CMR at 48 weeks and had durable progression-free survival (more than 400 days). At the time of analysis, 17 patients experienced disease progression, and 14 plasma samples were collected. Of those, 8 (57.1%) were positive for mutation in plasma. In five patients, plasma progression was observed prior to radiological progression. Exon 20 T790M was detected in five patients (detection rate: 62.5%).
Conclusion:
Among EGFR mutated NSCLC patients, liquid biopsy was a useful method to predict durable efficacy and progression. Applicability of liquid biopsy should be explored in further study.
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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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P2.07-035 - Correlation Between Immune-Related Adverse Events and Efficacy in Non-Small Cell Lung Cancer Treated with Nivolumab (ID 9403)
09:30 - 09:30 | Author(s): Y. Koh
- Abstract
Background:
Nivolumab has been established as a novel standard of care in patients with pre-treated non-small-cell lung cancer (NSCLC). Patients treated with nivolumab sometimes experience its unique adverse events, called immune-related Adverse Events (irAEs). Given the mechanisms of action of immune-checkpoint inhibitors (ICIs), occurrence of irAEs may potentially reflect antitumor response. Here, we report the clinical correlation between irAE and efficacy in NSCLC patients treated with nivolumab.
Method:
Between Dec 2015 and Feb 2017, 38 advanced NSCLC patients were treated with nivolumab at our institution. All patients were enrolled in our single-institutional observational cohort study (UMIN000024414). We divided the patients into two groups: irAEs group and no-irAEs group and evaluated the objective response rate (ORR), progression-free survival (PFS), and overall survival (OS). Efficacy was assessed by RECIST version 1.1, and toxicity was graded based on CTCAE version 4.0.
Result:
Of thirty-eight, median age was 68.5 (range, 49 to 86), 74% was male, 68% was non-squamous cell carcinoma, and 82% was performance status of 0-1. Among overall population, ORR was 23.7%, and median PFS was 91 days. Eleven patients (29%) experienced irAEs and median time to onset irAEs was 53 days (range, 14 to 213 days). There was no significant correlation observed between PD-L1 expression on tumor and occurrence of irAEs. Most common irAE was pneumonitis (n = 5) and others were hypothyroidism (n = 4), hyperthyroidism, hypopituitarism, hepatitis, rash and elevated thyroid stimulating hormone (one, each). Patients with irAEs had significantly higher efficacy compared with those without (ORR: 63.6% versus 7.4%, p < 0.01 (Fisher’s exact test), mPFS: not reached (NR) versus 49 days, p < 0.01 (log-rank test). Landmark analysis in patients who achieved progression free ≥ 12 weeks showed a similar trend (p = 0.07). Next, we performed additional analyses on correlation with specific irAEs. Patients with pneumonitis and those without demonstrated similar outcome (p = 0.95 (log-rank test)). With regard to endocrine irAEs, the similar result was also observed (p = 0.95 (log-rank test)).
Conclusion:
In our study, there was a correlation between irAEs and efficacy in NSCLC patients treated with nivolumab. Occurrence of specific irAE was not necessarily associated the efficacy.
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P3.01 - Advanced NSCLC (ID 621)
- Event: WCLC 2017
- Type: Poster Session with Presenters Present
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 10/18/2017, 09:30 - 16:00, Exhibit Hall (Hall B + C)
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P3.01-088b - Is Efficacy Result in Phase 2 Trial Replicated in Phase 3 Trial in Advanced NSCLC: A Meta-Analysis (ID 9125)
09:30 - 09:30 | Author(s): Y. Koh
- Abstract
Background:
Phase 3 trial has been mandatory to establish new treatment. However, molecular targeted agents were often approved based on phase 2 trials. There have not been fully investigated whether efficacy data in phase 2 would be replicated in phase 3.
Method:
We extracted phase 2 and 3 trials for advanced non-small cell lung cancer (NSCLC) using platinum doublet (Plt) or EGFR-tyrosine kinase inhibitor (TKI) monotherapy, published between 2005 and 2015. Overall response rate (ORR) and median progression-free survival (PFS) in each study were collected. We compared these data between phase 2 and 3.
Result:
155 phase 2 trials and 13 phase 3 trials were adopted as Plt trials, while 21 phase 2 trials and 6 phase 3 trials were adopted as TKI trials. Plt trials had larger sample size (median number of patients: 47 in phase 2, and 203 in phase 3) than TKI trials (median number of patients: 29 in phase 2, and 101.5 in phase 3). In Plt trials, median ORR and median of median PFS were 31% and 5.2 months in phase 2, while 27% and 4.7 months in phase 3. There was statistically significant difference between phase 2 and phase 3 in ORR and mPFS (p = 0.03 and 0.03, respectively). In TKI trials, median ORR and median of median PFS were 64.0% and 9.7 months in phase 2, while 64.5% and 10.9 months in phase 3. There were not significant difference between phase 2 and phase 3 either in ORR and mPFS (p = 0.88 and 0.31, respectively). Among TKI trials, equivalence of efficacy data between phase 2 and phase 3 was also investigated in ORR and mPFS, but not proved (p = 0.30 and 0.45, respectively).
Conclusion:
Efficacy of TKI in phase 2 trial was well replicated in phase 3 trial.
