Publication-only abstracts (abstract number preceded by an "e"), published in conjunction with the 2019 ASCO Annual Meeting but not presented at the Meeting, can be found online only.
Clinical outcomes of NSCLC patients with acquired RET rearrangement after resistance to osimertinib.
Metastatic Non-Small Cell Lung Cancer
Lung Cancer—Non-Small Cell Metastatic
2019 ASCO Annual Meeting
J Clin Oncol 37, 2019 (suppl; abstr e20626)
Author(s): Chang Lu, Jia-Tao Cheng, Jin Kang, Yi-Hui Yao, Xiang-Meng Li, Xuchao Zhang, Qing Zhou, Hai-Yan Tu, Yi-Long Wu, Jin-Ji Yang; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China
Background: Resistance mechanisms to osimertinib have raised growing concerns, but those with acquired RET rearrangement is poorly characterized. Methods: We retrospectively identified advanced, EGFR-mutant NSCLC (non-small-cell lung cancer) patients treated with osimertinib between April 9th, 2015 and November 1st, 2018 at our institute. Clinicopathologic features and clinical outcomes were analyzed. Subsequent genetic profiling was performed at the time of progression by next-generation sequencing (NGS). Overall survival (OS) since 1st line treatment was calculated from first-line treatment start to death or last follow up, and OS post-progression was calculated from osimertinib progression. Median follow-up time was 43.4 months. Results: In the 192 patients treated with osimertinib, 57 had follow-up NGS information after progression, and six harboured acquired RET rearrangement (11%, 6/57). For patients with RET rearrangements when progressed on osimertinib, OS since 1st line treatment (22.9m vs 59.5m, P = 0.021) and OS post-progression (2.1m vs 10.0m, P = 0.031) were significantly shorter compared with non-RET-rearranged cases, whereas no significant difference was found in demographics at the initial lung cancer diagnosis or progression-free survival (PFS) of osimertinib (12.1m vs 5.8m, P = 0.34). Among these six patients, one received best supportive care, two continued to use drugs targeting EGFR but deteriorating soon, three patients tried osimertinib combined with cabozantinib with one benefit from this combination approach. Conclusions:RET rearrangements could exist in EGFR-mutant NSCLC with acquired resistance to osimertinib and linked to inferior survival. Study on the molecular evolution and heterogeneity during treatment course are warranted for further therapeutic strategies.
|Non-RET-rearrangement at Progression (n = 51)||RET-rearrangement at Progression (n = 6)||P-value|
|Age at Dx (years)||56.1||59.5||0.558|
|Male||19 (37.3%)||1 (16.7%)||0.584|
|Female||32 (62.7&)||5 (83.3%)|
|ECOG PS at Dx|
|0-1||41 (80.4%)||4 (66.7%)||1|
|2-4||6 (11.8%)||1 (16.7%)|
|Histology at Dx|
|Adenocarcinoma||50 (98.0%)||6 (100%)||1|
|Adenosquamous carcinoma||1 (2.0%)||0 (0%)|