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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.

The continued osimertinib plus chemotherapy overcoming resistance after histologic transformation in EGFR-mutant lung adenocarcinoma treated with osimertinib.

Sub-category:
Metastatic Non-Small Cell Lung Cancer

Category:
Lung Cancer—Non-Small Cell Metastatic

Meeting:
2019 ASCO Annual Meeting

Abstract No:
e20615

Citation:
J Clin Oncol 37, 2019 (suppl; abstr e20615)

Author(s): Jin Kang, Xiang-Meng Li, Jia-Tao Cheng, Huajun Chen, Xuchao Zhang, Hai-Yan Tu, Qing Zhou, Yi-Long Wu, Jin-Ji Yang; Guangdong Lung Cancer Institute, Guangdong Provincial People's Hospital and Guangdong Academy of Medical Sciences, Guangzhou, China; Guangdong Lung Cancer Institute, Guangdong Provincial Key Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People's Hospital & Guangdong Academy of Medical Sciences, Guangzhou, China, Guangzhou, China

Abstract Disclosures

Abstract:

Background: Although the third-generation Epidermal Growth Factor Receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib is more potent, histologic transformation from lung adenocarcinoma to other histological types is still a mechanism of resistance in EGFR-mutant adenocarcinoma. Those with histologic transformation usually have poor prognosis. Hence, we focused on the unique molecular mechanism of histologic transformation after osimertinib and explore the strategy of treatment. Methods: Pathology was confirmed in 55 EGFR-mutant patients treated with osimertinib at baseline and disease progression. They were all lung adenocarcinoma at baseline. We established the patient-derived xenograft (PDX) mouse model from an EGFR-mutant adenocarcinoma transforming to neuroendocrine carcinoma. Preclinical efficacy of erlotinib versus osimertinib was evaluated in vivo. All the clinical data of these patients were analyzed. Results: The frequency of histologic transformation after resistance to osimertinib was 14.5% (8/55). Three of them were transformed to small-cell lung cancer totally, two transformed to complex small-cell lung cancer, two transformed to adenosquamous cell carcinoma and one transformed to neuroendocrine carcinoma without T790M mutation in which an PDX mouse model was successfully established. The genetic profiles of those transformed to small-cell lung cancer were characterized by Rb1, TP53 mutations, and PI3K/AKT/MTOR aberrances. Those transformed to adenosquamous carcinoma were characterized by KRAS amplification and EGFR amplification. The median progression-free survival (PFS) was not significantly different between the patients with histologic transformation and those without during the treatment of osimertinib (7.7 VS. 5.7 months, P = 0.763). One went on first-line osimertinib, added etoposide/ cisplatin (EP) chemotherapy meanwhile after progressive disease, and achieved minor response after 2 cycles. The other one received the treatment of EP + osimertinib + erlotinib, and acheived partial response with a PFS of 7 months without obvious toxicities. The PDX model showed more sensitivity to erlotinib than osimertinib. Conclusions: Continued osimertinib plus chemotherapy might be effective in overcoming the resistance. Particularly, the first-generation EGFR-TKI seems to be efficacious in histologically-transformed EGFR-mutant patients without T790M mutation. Further investigations of these patients and PDXs are warranted.

 
Other Abstracts in this Sub-Category:

 

1. Association of STK11/LKB1 genomic alterations with lack of benefit from the addition of pembrolizumab to platinum doublet chemotherapy in non-squamous non-small cell lung cancer.

Meeting: 2019 ASCO Annual Meeting Abstract No: 102 First Author: Ferdinandos Skoulidis
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

2. Real-world outcomes of patients with advanced non-small cell lung cancer (aNSCLC) and autoimmune disease (AD) receiving immune checkpoint inhibitors (ICIs).

Meeting: 2019 ASCO Annual Meeting Abstract No: 110 First Author: Sean Khozin
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

3. RELAY: A multinational, double-blind, randomized Phase 3 study of erlotinib (ERL) in combination with ramucirumab (RAM) or placebo (PL) in previously untreated patients with epidermal growth factor receptor mutation-positive (EGFRm) metastatic non-small cell lung cancer (NSCLC).

Meeting: 2019 ASCO Annual Meeting Abstract No: 9000 First Author: Kazuhiko Nakagawa
Category: Lung Cancer—Non-Small Cell Metastatic - Metastatic Non-Small Cell Lung Cancer

 

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