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Victor Lee
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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): Victor Lee
- 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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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
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P1.14-62 - Afatinib in EGFR TKI-Naïve Patients with EGFR Mutation-Positive NSCLC: Combined Analysis of Two Single-Arm Phase IIIb Studies (ID 1338)
09:45 - 18:00 | Author(s): Victor Lee
- Abstract
Background
First-line afatinib significantly improved progression-free survival (PFS) compared with platinum-doublet chemotherapy in patients with EGFR mutation-positive (EGFRm+; including uncommon mutations) NSCLC in two Phase III studies (LUX-Lung 3: median 11.1 vs 6.9 months, hazard ratio [HR]=0.58; p=0.001; LUX-Lung 6: 11.0 vs 5.6 months, HR=0.28; p<0.0001). First-line afatinib also significantly improved PFS compared with gefitinib in the Phase IIb LUX-Lung 7 study (11.0 vs 10.9 months, HR=0.73; p=0.017). However, some patients still receive chemotherapy as a first-line treatment choice in clinical practice. Here, we report a combined analysis of outcomes from two large Phase IIIb studies of afatinib in EGFR TKI-naïve patients treated in a setting similar to real-world practice.
Method
In both studies, EGFR TKI-naïve, including chemotherapy-pretreated, patients with locally advanced or metastatic EGFRm+ NSCLC received 40 mg/day afatinib until progressive disease or lack of tolerability (dose reduction was permitted [minimum: 20 mg/day]). Study 1 enrolled patients across eight European countries, and Russia, Israel and Australia; Study 2 enrolled patients from centres in China, Hong Kong, India, Singapore, and Taiwan. Interim (Study 1; data cut-off: 30 April 2018) and final (Study 2; data cut-off: 06 July 2018) data were used for this combined analysis of time to symptomatic progression (TTSP), PFS, objective response, and safety.
Result
A total of 1020 patients were treated with afatinib (female: 59%; Asian/White/other: 54%/46%/<1%; median age [range]: 61 years [25–89]; ECOG PS 0/1/2: 26%/69%/5%; common/uncommon EGFR mutations: 82%/18%; treatment line 1st/2nd/≥3rd: 69%/23%/8%; presence of brain metastases: 18%). Overall, median TTSP was 14.6 months (95% confidence interval [CI]: 13.8–15.8 months); median PFS was 12.9 months (95% CI: 11.6–13.7 months). Objective response rate was 52.7%. Adverse events (AEs; all grade/grade ≥3) occurred in 1012/556 (99%/55%) patients; serious AEs were reported in 366 patients (36%). The most common grade ≥3 AEs were diarrhoea (14%) and rash (9%). Any-cause AEs leading to dose reduction were reported in 412 (40%) patients. Treatment discontinuation due to afatinib-related AEs occurred in 54 patients (5%).
Conclusion
In this combined analysis of two large, prospective ‘real-world’ afatinib studies in EGFR TKI-naïve patient populations, which included patients treated with afatinib in later lines, patients with ECOG PS 2, patients with brain metastases, and patients with uncommon mutations, safety data were consistent with previous results seen in the LUX-Lung 3, 6, and 7 studies. Efficacy findings are also encouraging, with a median TTSP of 14.6 months.
