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Kwok Chi Lam
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MA16 - Prioritizing Use of Technology to Improve Survival of Lung Cancer Subgroups and Outcomes with Chemotherapy and Surgery (ID 142)
- Event: WCLC 2019
- Type: Mini Oral Session
- Track: Treatment in the Real World - Support, Survivorship, Systems Research
- Presentations: 1
- Now Available
- Moderators:Jair Bar, Navneet Singh
- Coordinates: 9/09/2019, 15:45 - 17:15, Interlaken (1988)
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MA16.02 - T790M Allelic Fraction Level Did Not Correlate Survival in T790M Positive NSCLC – Observations from an Early Access Program (Now Available) (ID 1809)
15:45 - 17:15 | Author(s): Kwok Chi Lam
- Abstract
- Presentation
Background
Osimertinib is an irreversible third-generation EGFR-TKI indicated for patients with metastatic EGFR T790M mutation positive NSCLC after progression of initial TKI therapy. An early access program (EAP) was started in 2015 providing ethical access of Osimertinib to patients with metastatic NSCLC running out of treatment options in Hong Kong. As some prior data suggested that T790M allele fraction (AF) correlated survival outcomes in patients receiving Osimertinib, we try to validate it with data from this EAP. Survival outcomes and safety data of Osimertinib in the real world practice under this EAP were also analysed. (NCT03219970)
Method
This retrospective analysis included EAP patients who had advanced or metastatic NSCLC harbouring EGFR T790M mutation that progressed on prior TKI ± chemotherapy. EAP subjects received Osimertinib at 80mg daily until disease progression, intolerable toxicities or death. The T790M mutation can be assessed by any approved molecular tests in any specimen types.
The AF levels in patients with T790M mutation confirmed by quantitative plasma genotyping (QPG) using ddPCR technique of the same vendor were retrieved. The primary objective was to assess the relationship of post-Osimertinib overall survival (OS) and T790M AF level. Secondary objectives included investigator-assessed response, time to discontinuation (TTD) of Osimertinib, safety (Osimertinib-related adverse events of special interest, AESIs) and OS of all EAP participants.
Result
From Sep 2015 to Feb 2017, 156 patients enrolled in the EAP and received treatment. At time of data cut-off (11 Oct 2018), 74 (47%) were alive. Median follow-up was 23.4 (range: 1–30) months, median age 62 years, 62% female, 26% ECOG PS ≥2, 96.8% with metastatic disease. Besides T790M, 56% of patients had exon 19 deletions and 41% had exon 21 L858R mutations.
Ninety-one patients had QPG using ddPCR method with AF data. OS, best response rate and TTD were not significantly related to T790M AF level as a continuous variable (p=0.20; hazard ratio 1.022, 95% CI 0.989 to 1.057), confirmed through sensitivity analysis with different AF threshold values.
The investigator assessed best response rate was 41.7% (65/156) and disease control rate was 62.2% (97/156). Median TTD was 15.77 (12.43, 18.98) months. Median OS was 21.88 (95% CI 19.14–26.21) months. AESIs were reported in 7.7% of patients overall: 5.8% QTc prolongation and 1.9% pneumonitis.
Conclusion
T790M AF level did not correlate with TTD and OS in this EAP cohort but the limitations should not be overlooked. The survival outcomes concurs other reported series.
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P2.01 - Advanced NSCLC (ID 159)
- Event: WCLC 2019
- Type: Poster Viewing in the Exhibit Hall
- Track: Advanced NSCLC
- Presentations: 1
- Moderators:
- Coordinates: 9/09/2019, 10:15 - 18:15, Exhibit Hall
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P2.01-99 - A Phase IIIb Open-Label Study of Afatinib in EGFR TKI-Naïve Patients with EGFR Mutation-Positive NSCLC: Final Analysis (ID 1671)
10:15 - 18:15 | Author(s): Kwok Chi Lam
- Abstract
Background
The safety and efficacy of afatinib, an orally administered irreversible EGFR TKI, have been demonstrated in patients with EGFR mutation-positive (EGFRm+) NSCLC in several Phase III clinical trials. However, prospective evidence supporting the clinical benefit of afatinib in the real-world setting is limited. Here, we report final data from a Phase IIIb open-label, multicenter trial evaluating safety and efficacy of afatinib in EGFR TKI-naïve Asian patients with locally advanced/metastatic EGFRm+ NSCLC, in a setting similar to real-world practice.
Method
EGFR TKI-naïve patients with locally advanced/metastatic EGFRm+ NSCLC were recruited from 34 sites in China, Hong Kong, India, Singapore, and Taiwan. Patients received 40 mg/day afatinib. Dose reduction to minimum 20 mg/day was permitted. Treatment continued until lack of clinical benefit as determined by the investigator. The primary and secondary safety endpoints were number of patients with serious adverse events (SAEs), and number of patients with drug-related AEs, respectively. The secondary efficacy endpoint was time to symptomatic progression (TTSP). Further endpoints included progression free survival (PFS), objective response, and duration of disease control.
Result
In total, 541 patients received afatinib. Baseline characteristics were representative of patients with EGFRm+ NSCLC (median age, 59 years; female, 52.9%; never smoked, 69.3%; EGFR mutations, common [Del19/L858R]/uncommon: 88.2% [48.2%/40.5%]/11.8%; ECOG performance status 0/1, 18.3%/79.7%; brain metastases, 19%). SAEs were reported in 164 patients (30.3%). 34 patients (6.3%) had drug-related SAEs, most commonly (grouped terms): diarrhea (1.8%), stomatitis (0.7%), and vomiting (0.7%). Drug-related AEs (DRAEs) of any grade were reported in 528 patients (97.6%). AEs leading to dose reduction occurred in 154 patients (28.5%); TRAEs leading to treatment discontinuation were reported in 17 patients (3.1%). Three patients experienced DRAEs leading to death (decreased appetite, dyspnea, and respiratory failure). Median TTSP was 14.0 months (95% confidence interval [CI]: 12.9, 15.9) and median PFS was 12.1 months (95% CI: 11.0, 13.6). Objective responses were reported in 312 patients (57.7%) by week 52; the median duration of response was 12.2 months (95% CI: 11.0, 13.5). 483 patients (89.3%) achieved disease control of median duration 13.6 months (95% CI: 12.1, 14.4).
Conclusion
Safety data for afatinib in this patient population were consistent with previously reported data, with no new safety signals. AEs were manageable and did not lead to discontinuation in most patients. This study also demonstrated the efficacy and clinical benefit of afatinib in Asian patients with locally advanced or metastatic EGFRm+ NSCLC in a near real-world setting.
