Cure Alveolar Soft Part Sarcoma International (iCureASPS)

Continuing EGFR-TKI beyond radiological progression in patients with advanced or recurrent, EGFR mutation-positive non-small-cell lung cancer: an observational study



Abstract

Background Some patients with advanced or recurrent, epidermal growth factor receptor (EGFR) mutation-positive (EGFR M+) non-small-cell lung cancer (NSCLC) continue to receive EGFR tyrosine kinase inhibitors (TKIs) beyond radiological progression.

Methods We analysed a cohort of 577 patients with EGFR M+ NSCLC, who had received a first-line EGFR-TKI. We classified patients according to clinical course and treatment patterns at Response Evaluation Criteria in Solid Tumors (RECIST) progressive disease (PD). We evaluated the period from RECIST PD to TKI discontinuation or clinical PD and also evaluated survival after RECIST PD and compared it between groups.

Results RECIST PD was documented in 451 cases, of which 283 (62.7%) were clinically stable. 186 (65.7%) discontinued and 97 (34.3%) continued the EGFR-TKI. In those who continued EGFR-TKI, median time between RECIST PD and clinical PD or TKI discontinuation was 5.1 months. Median survival after RECIST PD in patients who discontinued and continued EGFR-TKI after clinically stable RECIST PD was 14.6 and 15.3 months (p=0.5489), respectively. In multivariate analysis, continuing EGFR-TKI therapy, female gender, better performance status and exon 19 deletion subtype were likely positive predictive factors for survival after clinically stable RECIST PD.

Conclusion Our study suggests that some patients could benefit from receiving an EGFR-TKI beyond radiological progression.

This is an Open Access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial.

https://esmoopen.bmj.com/content/2/4/e000214

Although initial therapy with EGFR-TKI brings long progression-free survival (PFS) in patients with EGFR M+ NSCLC, other factors are also likely to contribute to their overall survival (OS). In studies evaluating patients undergoing EGFR-TKIs as first-line therapy, postprogression survival was longer than PFS.1–5 Moreover, postprogression survival was even longer than median survival time of patients without the mutation who were treated with cytotoxic drugs.

Discontinuation of EGFR-TKI and switch to chemotherapy with cytotoxic drugs is generally adopted for patients when radiological progressive disease (PD) is observed during treatment with the EGFR-TKI. However, due to the moderate adverse events associated with EGFR-TKIs compared with cytotoxic drugs, EGFR-TKI therapy is continued even after radiological PD in some cases (so-called ‘beyond PD’ administration).6 Several retrospective studies have tried to show the efficacy of EGFR-TKI therapy beyond PD; however, these studies excluded patients whose disease was rapidly progressing and who could not continue EGFR-TKI therapy from the ‘beyond PD’ group.7–10 Therefore, patients receiving an EGFR-TKI could potentially have moderate disease progression and better survival. EGFR-TKIs after radiological PD used in combination with a cytotoxic drug could not show effectiveness.11

In this study, we analysed the clinical management and course of patients with advanced EGFR M+ NSCLC whose cancer had become resistant to first-line EGFR-TKI therapy. We evaluated the impact of the continuation of EGFR-TKIs on the outcomes of the patients who were judged to have Response Evaluation Criteria in Solid Tumors (RECIST)-based, that is, radiological PD.