Next-Generation Sequencing Liquid Biopsy-Guided Osimertinib Rechallenge in EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients

Fuchs, Vered; Kian, Waleed; Lichtenberg, Rachel; Cooper, Jonah M.; Remilah, Areen A; Levin, Daniel; Peled, Nir; Roisman, Laila C.

doi:10.1007/s40261-021-01116-4

Cited by 8 publications

(7 citation statements)

References 20 publications

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“…Rechallenge with osimertinib has been described as an optional treatment for patients with acquired resistance following prior osimertinib therapy. 18 , 19 , 20 , 21 , 22 , 23 Metro et al 21 documented the success of osimertinib rechallenge against EGFR T790M‐positive NSCLC in a patient who progressed after sequenced osimertinib and chemotherapy. A study that included 15 people with EGFRm NSCLC rechallenged with osimertinib after interval therapy, showing a response rate of 33% and a median progression‐free survival (PFS) of 4.1 months.…”

Section: Discussionmentioning

confidence: 99%

“…A study that included 15 people with EGFRm NSCLC rechallenged with osimertinib after interval therapy, showing a response rate of 33% and a median progression‐free survival (PFS) of 4.1 months. 23 Recently, Fuchs et al 19 described a case series of six patients with EGFRm NSCLC resistant to erlotinib, finding that the median duration of treatment was 5.0 months, and the median overall survival (OS) was 45.0 months. In addition, the combination of osimertinib rechallenge and bevacizumab showed benefits and resulted in significantly longer PFS and OS compared to chemotherapy plus bevacizumab in patients with acquired resistance to osimertinib 18 Comparatively, our patient received chemotherapy intervention and was then directed to clinical trials after osimertinib resistance.…”

Section: Discussionmentioning

confidence: 99%

“…Rechallenge with osimertinib has been described as an optional treatment for patients with acquired resistance following prior osimertinib therapy 18–23 . Metro et al 21 documented the success of osimertinib rechallenge against EGFR T790M‐positive NSCLC in a patient who progressed after sequenced osimertinib and chemotherapy.…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Survival benefit of combinatorial osimertinib rechallenge and entrectinib in an EGFR‐mutant NSCLC patient with acquired LMNA‐NTRK1 fusion following osimertinib resistance

Wang

Zhu

et al. 2022

Respirology Case Reports

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Acquired resistance to osimertinib is inevitable and heterogeneous despite its documented efficacy against EGFR‐mutated non‐small cell lung cancer (NSCLC). Subsequent therapeutic options assume the dominant form of the resistance mechanism; however, the more rare oncogenic driver, NTRK1 fusion, has also reportedly conferred osimertinib resistance. Nevertheless, clear‐cut options when NSCLCs are driven by EGFR mutation and the subsequent NTRK fusion are lacking. This is a case of NSCLC wherein exon 19 deletion in EGFR (19del) and acquired LMNA‐NTRK1 fusion were accompanied by the persistence of EGFR T790M. The patient underwent peritoneal metastasis after multiple targeted therapies: gefitinib, osimertinib, chemotherapy, and anlotinib plus docetaxel (in clinical trials). Osimertinib was subsequently re‐administered with the NTRK fusion inhibitor entrectinib, resulting in remission of peritoneal metastases even after slow progression of pancreatic metastasis over the following 5 months. An extensive literature review to identify the efficacies of therapies for NTRK fusion as the means to acquired resistance to EGFR TKIs revealed that blocking both the EGFR mutation and the subsequent NTRK fusion can provide clinical benefits following EGFR TKIs resistance; however, the efficacy and safety of combination therapies must be further investigated. To precisely manage EGFR‐mutated NSCLCs, it is also essential to identify the resistance mechanisms by repeating biopsies.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Survival benefit of combinatorial osimertinib rechallenge and entrectinib in an EGFR‐mutant NSCLC patient with acquired LMNA‐NTRK1 fusion following osimertinib resistance

Wang

Zhu

et al. 2022

Respirology Case Reports

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“…This could certainly improve treatment strategies, especially in later lines. To back this concept up, Fuchs and colleagues used liquid biopsy (Guardant260) as a tool to determine whether an EGFR-mutated NSCLC patient pretreated with osimertinib could be rechallenged with the same target therapy after interval chemotherapy (14). At the time of acquired resistance on osimertinib the liquid biopsy identified the parental EGFR exon 19 deletion plus T790M and C797S mutations in a patient.…”

Section: Editorialmentioning

confidence: 99%

Tracking and tackling the tumor dynamics clonal evolution: osimertinib rechallenge after interval therapy might be an effective treatment approach in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)

Metro¹,

Bonaiti²,

Birocchi³

et al. 2022

J Thorac Dis

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“…Although underdiagnosed, about 10% of EGFR-mutated NSCLC patients experience LM during systemic TKI therapy, leading to dismal outcomes with a median survival of fewer than 6 months ( 4 , 5 ). In clinical practice, many physicians frequently provide a chemotherapy or immunotherapy break followed by EGFR-TKI retreatment ( 3 , 6 ). However, the optimal treatment for patients with EGFR-mutated NSCLC and LM that develops after EGFR-TKI therapy failure remains unclear.…”

Section: Introductionmentioning

confidence: 99%

Case report: Rechallenge with EGFR–TKIs after immunotherapy in EGFR–mutated non–small cell lung cancer with leptomeningeal metastasis

et al. 2022

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Rechallenge of epidermal growth factor receptor-tyrosine kinase inhibitors (EGFR-TKIs) after PD-1 blockade failure was an effective therapy for non-small cell lung cancer (NSCLC) patients with resistance to EGFR-TKIs. The third-generation TKIs, like osimertinib and furmonertinib, can reach higher concentration in the cerebrospinal fluid (CSF) than other TKIs, and exhibit a beneficial effect in NSCLC patients with leptomeningeal metastases (LM) harboring sensitive EGFR mutation. Here, we report that two-stage IV pulmonary adenocarcinoma patients with LM harboring an EGFR L858R mutation benefit from the third-generation EGFR-TKIs rechallenge after immune checkpoint inhibitor (ICI) and anti-angiogenic agent combination therapy. Complete response (CR) to partial response (PR) of central nervous system (CNS) response was achieved immediately after the administration of furmonertinib and osimertinib. We conducted next-generation sequencing (NGS) and IHC to elucidate the evolution of driver mutations and the immune microenvironment. In conclusion, these two cases might provide a therapeutic strategy for further clinical practice. More research was needed to elucidate the resistance mechanisms and improve current treatment strategies in EGFR-mutated patients with LM.

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Next-Generation Sequencing Liquid Biopsy-Guided Osimertinib Rechallenge in EGFR-Mutated Advanced Non-Small-Cell Lung Cancer Patients

Cited by 8 publications

References 20 publications

Survival benefit of combinatorial osimertinib rechallenge and entrectinib in an EGFR‐mutant NSCLC patient with acquired LMNA‐NTRK1 fusion following osimertinib resistance

Survival benefit of combinatorial osimertinib rechallenge and entrectinib in an EGFR‐mutant NSCLC patient with acquired LMNA‐NTRK1 fusion following osimertinib resistance

Tracking and tackling the tumor dynamics clonal evolution: osimertinib rechallenge after interval therapy might be an effective treatment approach in epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC)

Case report: Rechallenge with EGFR–TKIs after immunotherapy in EGFR–mutated non–small cell lung cancer with leptomeningeal metastasis

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