Effectiveness of EGFR‐TKI rechallenge immediately after PD‐1 blockade failure

Abstract

Background There is currently insufficient information available on effective therapies that can be administered to patients with non‐small cell cancer (NSCLC) who develop resistance to epidermal growth factor receptor‐tyrosine kinase inhibitors (EGFR‐TKIs). However, sequential treatment via programmed death‐1 (PD‐1) blockade followed by EGFR‐TKI rechallenge is suggested to improve the therapeutic efficacy in such patients. Methods A total of 75 patients with advanced NSCLC harboring sensitive EGFR mutations treated with afatinib, erlotinib, or gefitinib after EGFR‐TKI treatment failure were retrospectively analyzed. Among them, 13 patients were treated with EGFR‐TKI rechallenge immediately after the failure of PD‐1 blockade therapy (experimental group) and the remaining 62 patients did not receive PD‐1 inhibitor therapy before EGFR‐TKI rechallenge (control group). Blood samples were collected at two time points; before the initiation of anti‐PD‐1 therapy and at EGFR‐TKI rechallenge. Results The objective response rates of EGFR‐TKI rechallenge in the experimental and control groups were 46.1% and 16.1%, respectively, with a significant difference (p = 0.026). In the experimental group, the median progression‐free survival (PFS) and overall survival (OS) after EGFR‐TKI rechallenge were 5.0 and 25.0 months, respectively, and no statistically significant difference in the percentage of lymphocytes before immune checkpoint inhibitor (ICI) therapy and EGFR‐TKIs was observed in patients with partial response (PR) and without PR after EGFR‐TKI rechallenge. In particular, the sequential treatment of PD‐1 blockade therapy followed by EGFR‐TKI rechallenge was consecutively repeated three times in two out of 13 patients in the experimental group, and EGFR‐TKI rechallenge consecutively for the third time yielded a PR without increased toxicities. Conclusions EGFR‐TKI rechallenge immediately after PD‐1 blockade treatment was identified as an effective therapy for NSCLC patients with resistance to EGFR‐TKIs.

Treatment Patterns and Adverse Event-Related Hospitalization Among Patients with Epidermal Growth Factor Receptor (EGFR)-Mutated Metastatic Non-small Cell Lung Cancer After Treatment with EGFR Tyrosine Kinase Inhibitor and Platinum-Based Chemotherapy Regimens

“…Continuation of EGFR TKIs beyond disease progression is recommended by the current NCCN Guidelines for patients who experience disease progression upon TKI discontinuation (flare phenomenon) in which case the EGFR TKI might be restarted [ 14 ]. Rechallenge with EGFR TKIs has also been discussed in the literature [ 16 – 19 , 31 , 32 ]. In their review of EGFR resistance mechanisms in lung cancer, Tumbrink et al noted that several on-target EGFR mutations that promote resistance to osimertinib remain sensitive to first-generation and second-generation EGFR inhibitors and suggest that rechallenging patients with these agents could be an effective strategy [ 16 ].…”

“…Rechallenging with EGFR TKIs in selected patients may improve tolerability relative to immune checkpoint inhibitor or cytotoxic therapies [ 24 , 33 ]. Additional literature has discussed a rechallenge with EGFR TKIs, often as case studies or in small cohorts, noting that this approach is occasionally effective [ 17 – 19 , 31 , 32 ]. While a rechallenge may be effective in some cases, it highlights the lack of effective alternative treatment options in later LOTs as well as our limited knowledge on the optimal sequence of EGFR TKIs among patients with EGFR-mutated mNSCLC [ 34 ].…”

“…Non-platinum chemotherapies (e.g., docetaxel with or without ramucirumab, pemetrexed [for adenocarcinoma], albumin-bound paclitaxel, or gemcitabine if not previously given) are often recommended despite limited evidence on clinical efficacy and treatment benefit [ 14 , 16 – 19 ]. An understanding of the real-world treatment patterns and outcomes of later lines of therapy (LOTs) will be informative to both healthcare payers and providers and will help evaluate how well existing treatments are meeting the needs of patients with mNSCLC.…”

Rechallenge with EGFR-TKI after failure of immunotherapy is considered an effective treatment for advanced lung adenocarcinoma patients with EGFR exon 19 deletion: a case report

“…We searched for EGFR-TKI rechallenge following immunotherapy failure in the literature. In a study byKaira et al ( 15 ), a retrospective analysis of 75 patients with advanced NSCLC and sensitive EGFR mutations revealed that approximately half of the patients had a good response to EGFR-TKI rechallenge, while approximately 25% of all patients had no response to EGFR-TKI rechallenge following the failure of immunotherapy. In the study, two cases were reported in which a dramatic response upon EGFR-TKI rechallenge was achieved.…”

Efficacy of Lenvatinib Combined with PD-1 Inhibitor versus Sorafenib and PD-1 Inhibitor with or Without TACE for Hepatocellular Carcinoma with Extrahepatic Metastasis

“…Firstly, the combination could produce synergistic effect by regulating the vasculature and the immune microenvironment of tumors. 15 , 16 Secondly, the combination may enhance antigen presentation in dendritic cells. 16 Thirdly, the combined use of these drugs can promote T cell activation in the priming phase, as well as stimulate the mobilization of T cells from the lymph nodes to the tumor microenvironment.…”