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Jiyun Lee
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MA04 - Health Policy and the Real World (ID 217)
- Event: WCLC 2020
- Type: Mini Oral
- Track: Health Services Research/Health Economics
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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MA04.06 - Clinical Characteristics and Outcomes in Advanced KRAS Mutant NSCLC – A Multi-Centre Collaboration in Asia (ATORG-005) (ID 3475)
16:45 - 17:45 | Presenting Author(s): Jiyun Lee
- Abstract
- Presentation
Introduction
KRAS driver mutations in advanced NSCLC have long been considered to be undruggable. However, promising efficacy data from early phase trials of novel therapies targeting KRAS have renewed focus on KRAS as an oncogenic driver. There is limited data on the prognostic and predictive significance of KRAS mutation subtypes. We present an interim analysis of a real world observational multi-centre study of advanced KRAS mutant NSCLC patients from five countries in Asia, conducted by the Asian Thoracic Oncology Research Group (ATORG).
Methods
Patients with advanced KRAS mutant NSCLC treated with at least one line of systemic therapy at tertiary centres in five Asian countries (China, India, Japan, Singapore, South Korea) between Jan 2014 and Dec 2018 were included. Baseline clinical characteristics, molecular profile and treatment outcomes were collected (median follow-up 35.5 months, 95%CI 28.7-50.3).
Results
A total of 155 patients were included in this interim analysis, with median age at advanced stage diagnosis 63 years (interquartile range [IQR] 56-70), 93% were ECOG 0-1, 70% were male and 64% were current or ex-smokers. In terms of ethnicity, 39% were Korean, 36% were Chinese, 15% were Japanese, 8% were Indian and 2% were Malay. Baseline histology was adenocarcinoma in 90%, squamous cell carcinoma in 4% and other histologies in 6%. KRAS mutation was detected by NGS in 141 (91%) patients, Sanger sequencing in 12 (8%) patients and RT-PCR in 2 (1%) patients. KRAS G12C (26%) was most common, followed by G12D (23%) and G12V (21%). The incidence of KRAS G12C mutation in patients with a smoking history was 35/99 (35%) compared with 6/56 (11%) in patients without any smoking history. Co-alterations were found with EGFR mutations (14%), ALK fusions (1%), ROS1 fusions (1%) and BRAF mutations (3%). PD-L1 TPS was 0% in 22%, 1-49% in 19%, ≥50% in 14% and unknown/not tested in 45%. Brain metastases were present at advanced stage diagnosis in 25% and lifetime prevalence was 35%. Patients received a median 2 lines of therapy. First-line systemic therapy consisted of chemotherapy alone (66%), targeted therapy (15%) or other therapies (19%). Median time to next treatment (TTNT) on first-line chemotherapy alone was 7.3 months (95%CI 5.0-9.5). Overall, the median TTNT for first-line and second-line therapy was 7.7 (95%CI 6.5–10.0) and 7.0 (95%CI 5.3–10.9) months, respectively. 63% of patients had died, and 37% of patients were still alive or lost to follow-up at the time of data cut-off. Median OS for the overall cohort was 21.6 months (95%CI 15.9-27.6). Median OS was greater in immunotherapy treated (alone or in combination at any line; 45%) versus non-immunotherapy treated (55%) patients (27.6 [95%CI 19.1-37.9] months versus 15.4 [95%CI 10.3-23.7] months, HR 1.8, 95%CI 1.2-2.7, logrank p=0.005).
Conclusion
In Asian KRAS mutant NSCLC, duration of first-line therapy and survival outcomes remain poor – emphasising the need for greater therapeutic options for patients with a KRAS driver mutation. Additional sites/countries are planned and recruitment to this study is ongoing.
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P76 - Targeted Therapy - Clinically Focused - EGFR (ID 253)
- Event: WCLC 2020
- Type: Posters
- Track: Targeted Therapy - Clinically Focused
- Presentations: 1
- Moderators:
- Coordinates: 1/28/2021, 00:00 - 00:00, ePoster Hall
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P76.15 - Osimertinib Improved Overall Survival in mEGFR NSCLC Patients With Leptomeningeal Metastases Regardless of T790M Mutational Status (ID 1161)
00:00 - 00:00 | Presenting Author(s): Jiyun Lee
- Abstract
Introduction
Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), demonstrated superior penetration of the blood-brain barrier, compared with first- or second-generation EGFR TKIs. However, previous studies have not evaluated whether treatment with osimertinib leads to improved overall survival (OS) for EGFR-mutated NSCLC patients with leptomeningeal metastases (LM) compared with those not treated with osimertinib.
Methods
From October 2008 to October 2019, patients with EGFR-mutated NSCLC and cytologically confirmed LM were analyzed for OS according to osimertinib treatment and T790M mutational status. OS was defined as the time from diagnosis of LM to death due to any cause.
Results
For the 351 LM patients included in analysis, the median OS (mOS) was 8.1 months (95% confidence interval [CI] 7.2–9.0). T790M mutation was detected in 88 of 197 patients tested, and a total of 110 patients were treated with osimertinib after LM. No significant difference in mOS was demonstrated according to T790M mutational status (10.1 months [95% CI 4.31–15.82] vs. 9.0 [95% CI 6.81–11.21], P = 0.936). However, patients treated with osimertinib showed a superior OS of 17.0 months (95% CI 15.13–18.94) compared with those not treated with osimertinib who showed a mOS 5.5 months (95% CI 4.34–6.63) regardless of T790M mutational status (Hazard ratio 0.36; 95% CI 0.28–0.47, P <0.001). This was a significant survival benefit even compared with those who were never treated with osimertinib but with first-/second-generation EGFR TKIs showing a mOS of 8.7 months (95% CI 7.01–10.39).
Conclusion
Osimertinib is a promising treatment option for EGFR-mutated NSCLC with LM regardless of T790M mutational status.
