Here, we conducted a retrospective study to assess 375 patients whose initial biopsy indicated a TKI-sensitizing mutation (either EGFR 19del or L858R) and who developed PD after treatment with first-generation TKIs, and assayed for T790M status.
Tumours from 31 patients with metastatic colorectal cancer who had either an objective response (n=10) or stable disease or progressive disease (n=21) after treatment with cetuximab or panitumumab were screened for genetic changes in EGFR or its immediate intracellular effectors.
EGFR mutation was observed in 10 of 27 and significantly more frequently observed in the posttreatment samples from patients with a partial response or stable disease than in those from patients with progressive disease (p = 0.006).
In this work, we prospectively recruited 68 patients with metastatic EGFR-mutated NSCLC who have developed progressive disease after first-line TKI with or without subsequent TKI and/or other systemic therapy.
He developed progressive disease in liver 4 months later, and the biopsy of liver metastases showed neuroendocrine carcinoma maintained the same EGFR mutation.
Heterogeneous responses were seen in patients with progressive disease as best response with a marked size decrease of the biopsied (cMET amplification positive) lesion and progression of other lesions. cMET amplification was not always mutually exclusive with other EGFR TKI resistance mechanisms.
In patients with clinical benefit (progressive disease after 8 weeks), ctDNA testing revealed previously undetected mutations in RAS/BRAF (71%) and EGFR (47%), which often emerged polyclonally.
Plasma beta-arrestin-1 levels were considerably higher in lung cancer patients than in healthy donors and were higher in patients who later experienced a progressive disease than in patients showing complete/partial response following EGFR inhibitor therapy.
Total duration of EGFR-TKI treatment before rebiopsy, TKI-free interval, EGFR-TKI treatment history immediately before rebiopsy, continuation of initial EGFR-TKI beyond progressive disease, progression-free survival after initial TKI treatment, and rebiopsy site (other than fluid samples) significantly influenced T790M status.
We discuss the interplay between ERBB/SRC signaling, and polycystins and their depending signaling, with emphasis on thes changes that affect cell proliferation in cyst expansion, as well as the inflammation-associated fibrogenesis, which characterizes progressive disease.
This study aimed to analyze the characteristics and outcomes of patients suffering from non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor mutations (EGFRm+) receiving gefitinib who remained clinically stable following confirmation of progressive disease (PD) using Response Evaluation Criteria in Solid Tumors (RECIST) (R-PD) and identify those who benefited from tyrosine kinase inhibitor therapy beyond PD.
Presented here is a case of stage IV NSCLC harboring an uncommon EGFR exon 20 insertion mutation that was maintained at minimal progressive disease for 54 months, with 36 months on the second-generation TKI afatinib.
Blood samples were collected at baseline and every treatment cycle and analyzed for 31 RAS, RAF, and EGFR mutations until progressive disease or censoring using droplet digital PCR.
Twenty-three patients with lung cancer with progressive disease after EGFR-TKI treatment and 21 patients who had never been treated with EGFR-TKIs were studied.
Our results suggest that the continuous inhibition of epidermal growth factor receptor phosphorylation by erlotinib after progressive disease enhances the antitumor activity of chemotherapy.