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Kevin Lee Min Chua
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ES03 - Understanding and Treating Oligometastatic Diseases (ID 161)
- Event: WCLC 2020
- Type: Educational Session
- Track: Locoregional and Oligometastatic Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 10:30 - 11:30, Scientific Program Auditorium
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ES03.06 - Radiation as a Component of Treatment for Oligometastatic Disease (ID 3980)
10:30 - 11:30 | Presenting Author(s): Kevin Lee Min Chua
- Abstract
- Presentation
Abstract not provided
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OA06 - Updates on EGFR Targeted Perioperative Therapy and Precision Adjuvant Chemotherapy (ID 118)
- Event: WCLC 2020
- Type: Oral
- Track: Early Stage/Localized Disease
- Presentations: 1
- Moderators:
- Coordinates: 1/29/2021, 16:45 - 17:45, Scientific Program Auditorium
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OA06.05 - Molecular and Clinical Features Associated with Relapse in Early Stage EGFR-Mutated NSCLC: A Single Institution Knowledge Bank (ID 3813)
16:45 - 17:45 | Author(s): Kevin Lee Min Chua
- Abstract
- Presentation
Introduction
The ADAURA study showed significant reduction in risk of disease recurrence/death with adjuvant osimertinib for Stage IB–IIIA resected EGFR-mutated NSCLC. However, due to early unblinding of the study coupled with paucity of data on patterns of relapse and absence of long-term survival data, the cost:benefit ratio of adjuvant osimertinib remains uncertain. We sought to determine molecular and clinical features that impact outcomes in early stage EGFR-mutated NSCLC.
Methods
Consecutive patients with AJCC v7.0 Stage IA–IIIA resected EGFR-mutated NSCLC diagnosed between 1/1/2010-30/6/2018 who underwent curative surgery at National Cancer Centre Singapore were included. Patient demographics, treatment history were collated and long-term follow up was available for 91.6% of the cohort. We analyzed 2-year DFS by Kaplan-Meier method. In exploratory analysis, exome and/or RNA-sequencing was performed in a subset of 96 patients.
Results
A total of 396 patients were included. Median age at diagnosis 64 years, 63.6% were females and 80.6% were non-smokers. Stage IA comprised 42.2%, Stage IB 23.2%, Stage 2 15.6% and Stage 3A 18.7%. Exon19 deletion mutations comprised 48.7%; while L858R 37.9%. Of the 376 patients (94.9%) who underwent lobectomy, 88.9% had a complete resection. Adenocarcinomas made up 98.5% of the cohort, of which acinar subtype was predominant (61.9%). Majority of Stage II (53.2%) and III (73.0%) patients received adjuvant chemotherapy. 8.6% of patients received post-operative radiotherapy.
At a median follow up of 46 months, 168 patients (42.4%) had recurrent disease. Of the 168 patients with recurrent disease, 41.7% had received adjuvant systemic treatment and 8.9% of them had received neoadjuvant treatment. Median time to recurrence was 17 months. 2-year DFS rate was 79.6% for Stage I, 57.3% for Stage II and 47.1% for Stage III. At the time of analysis, 94 patients had died and 62.8% were attributed to NSCLC. Of the 254 patients with at least 3 years of follow up, 120 have relapsed–representing 35/167 of Stage IA (21.0%), 22/92 (23.9%) Stage IB, 24/62 (38.7%) Stage II and 39/74 (52.7%) Stage IIIA. In terms of sites of disease at relapse, 32.1% had locoregional relapse and 23.2% had intracranial relapse. Lung was the most common site of distant metastases at 47.6%, followed by pleura (20.8%) and bone (17.3%). In a subset of patients with exome and RNA-sequencing performed, we employed various feature selection methods on 69 pre-selected clinical, pathological and molecular features that may contribute to RFS. We identified RHPN2 mutation, CTNBB1 mutation, micropapillary subtype and loss of heterozygosity in human leucocyte antigen as negative prognostic features when controlling for stage and other potential confounding factors.
Conclusion
Our study confirms that despite curative resection and adjuvant chemotherapy, recurrence rates remain high in early stage EGFR-mutated NSCLC, and worrisomely even in stage IA. The 2-year RFS in our cohort is comparable to the control arm of ADAURA, with almost a quarter of patients suffering from intracranial relapse. Our exploratory analysis highlights how molecular features can complement clinical features to improve risk stratification. Further studies are needed to elucidate individualized surveillance and adjuvant treatment strategies for early stage EGFR-mutated NSCLC.
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