Exceptional Response of a Large and Symptomatic EGFR-Mutant Brain Metastasis to Osimertinib: Case Report and Review of the Literature.
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ABSTRACT:
SUBMITTER: Zeeshan Ozair M
PROVIDER: S-EPMC8169075 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Exceptional Response of a Large and Symptomatic EGFR-Mutant Brain Metastasis to Osimertinib: Case Report and Review of the Literature.
Zeeshan Ozair M M Giantini Larsen Alexandra M AM Eng Juliana J Moss Nelson S NS
JCO precision oncology 20210401
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Project description:The efficacy of first-and second-generation epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in NSCLC patients with the EGFR L861Q mutation has been studied previously. However, there is little evidence on the efficacy of osimertinib in NSCLC patients with uncommon mutations. Here, we report the case of a 68-year-old man with advanced NSCLC with concurrent EGFR L861Q mutation as well as TP53 and RB1 mutations. The patient was treated with osimertinib as first-line therapy and achieved a remarkable progression-free survival of 15 months. His symptoms were significantly alleviated and the dose was well tolerated. The findings of the present study indicate that osimertinib might be a good treatment option for NSCLC patients with the L861Q mutation.
| S-EPMC8445031 | biostudies-literature
Project description:Third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitors (TKIs) have revolutionized the standard treatment for EGFR T790M-positive non-small cell lung cancer (NSCLC). Osimertinib is one of the third-generation EGFR-TKIs and is currently the most advanced in clinical development. Interstitial lung disease (ILD) is a potentially fatal side effect of osimertinib use. Successful rechallenge with the second-generation TKI afatinib following osimertinib-induced ILD has been reported. However, few reports have discussed the safety and efficacy of third-generation TKI rechallenge in this patient population. In this paper, a case of lung adenocarcinoma is retrospectively analyzed, and the relevant literature is reviewed. The patient was initially diagnosed with early lung cancer, for which surgical treatment was performed. The postoperative diagnosis indicated stage IB (pT2N0M0) right lung adenocarcinoma. Genetic testing (amplification-refractory mutation system) revealed EGFR exon 19 deletion. More than 2 years after surgery, multiple metastases occurred in both lungs, so gefitinib (250 mg per day) was administered. However, 6 months after the start of gefitinib treatment, the tumor progressed. Lung tumor biopsy was performed for genetic testing (NGS) and an EGFR T790M mutation was observed. Subsequently, second-line treatment with osimertinib (80 mg per day) was given for 3 months. The evaluated response suggested a partial response (PR) with the occurrence of grade 3 ILD. Pemetrexed plus bevacizumab chemotherapy was subsequently administered, resulting in stable disease. However, following a severe drug reaction after six courses, the patient's chemotherapy was discontinued. Another third-generation TKI, almonertinib (110 mg per day), was rechallenged based on no ILD having been reported in a phase I/II study of this drug. After 4 months of almonertinib administration and 6 months without ILD recurrence, partial remission was attained. This is the first report of successful treatment with almonertinib after osimertinib-induced ILD. The results suggested that almonertinib had a significant effect in patients with EGFR T790M mutation, with fewer side effects and better survival benefits for patients with advanced lung cancer.
| S-EPMC8263887 | biostudies-literature
Project description:BACKGROUND:Osimertinib, a third-generation epidermal growth factor receptor tyrosine kinase inhibitor, is selective for both epidermal growth factor receptor tyrosine kinase inhibitor-sensitizing and T790M resistance mutations. Almost all patients who initially respond to an epidermal growth factor receptor tyrosine kinase inhibitor subsequently report disease progression. Epidermal growth factor receptor-dependent resistance mechanisms, bypass pathway activation, and histological transformation have been reported with osimertinib therapy. CASE PRESENTATION:We report a case of a 64-year-old Asian man with epidermal growth factor receptor T790M-positive adenocarcinoma that transformed to epidermal growth factor receptor T790M-negative large-cell neuroendocrine carcinoma after osimertinib therapy. A prompt rebiopsy revealed a rare mechanism of resistance to epidermal growth factor receptor tyrosine kinase inhibitor, and subsequently treatment with carboplatin and etoposide was effective. CONCLUSIONS:Despite the promising emergence of circulating tumoral DNA testing, this case report emphasizes the importance of rebiopsy of a progressive epidermal growth factor receptor-mutant tumor.
| S-EPMC7412784 | biostudies-literature
Project description:Although lung cancer rarely metastasizes to the breast, we report a case of breast metastasis from lung adenocarcinoma harboring an epidermal growth factor receptor mutation. This breast metastasis was initially considered recurrent breast cancer and was later diagnosed based on histopathological and molecular examinations as metastasis from lung cancer.
| S-EPMC6098998 | biostudies-literature
Project description:BackgroundOsimertinib-the third-generation epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor (TKI)-has been widely used as a first-line treatment for patients with metastatic EGFR-mutant non-small cell lung cancer (NSCLC). Osimertinib demonstrated central nervous system activity in patients with brain metastasis; however, its efficacy against other distant metastatic organs, including bone and liver, remains unclear. Therefore, we retrospectively analyzed the clinical efficacy of osimertinib in these patients in comparison to other EGFR-TKIs.MethodsClinical data of patients with advanced NSCLC receiving gefitinib/erlotinib (n = 183), afatinib (n = 55), or osimertinib (n = 150) at five medical institutions were retrospectively assessed for progression-free survival (PFS), overall survival (OS), and best overall response rate (ORR).ResultsIn univariate and multivariate analyses, most distant metastases, including the brain and bone, were unrelated to the therapeutic efficacy of osimertinib, although liver metastasis and L858R mutation were independently associated with shorter PFS. PFS and OS in patients with liver metastases were significantly shorter than those in patients without liver metastases (PFS: 7.4 vs. 19.7 months, OS: 12.1 months vs. not reached, respectively). Osimertinib provided significantly longer PFS in patients with brain or bone metastasis and exon 19 deletion than the other EGFR-TKIs. The PFS of patients with liver metastases was not significantly different among the three EGFR-TKI groups. Furthermore, the ORR of osimertinib in patients with liver metastases was significantly attenuated, and the effectiveness was similar to 1st- or 2nd -generation EGFR-TKIs.ConclusionOsimertinib provided better clinical benefits than 1st- and 2nd-generation EGFR-TKIs for patients with EGFR-mutant NSCLC, particularly those with brain or bone metastases and exon 19 deletion; however, its efficacy against liver metastasis was remarkably attenuated. New therapeutic developments for patients with EGFR-mutant NSCLC with liver metastases are needed.
| S-EPMC9195197 | biostudies-literature
Project description:BackgroundTyrosine kinase inhibitors (TKIs) have changed the treatment landscape for patients with advanced non-small cell lung cancer (NSCLC) found to have oncogene-driven activating epidermal growth factor receptor (EGFR) mutations. Whilst there have been a handful of case reports of sensitivity to first-generation TKIs in EGFR L861R mutations, the efficacy of the third-generation TKI osimertinib in NSCLC patients with EGFR L861R and EGFR exon 18 deletion-insertion mutations is limited.Case descriptionWe report two patients from our institution with uncommon EGFR mutations treated with first-line osimertinib. Our first patient, a 72-year-old male with metastatic lung adenocarcinoma was identified to harbour a rare EGFR L861R mutation and was commenced on osimertinib. After a follow-up period of 18 months, the patient is continuing to experience treatment benefit with imaging showing a good partial response. The second patient, a 60-year-old male also with metastatic lung adenocarcinoma and an EGFR exon 18 deletion-insertion mutation achieved a partial response for 6.6 months. Upon progression, he was commenced on carboplatin and pemetrexed chemotherapy however died from subsequent pneumonia. He had an overall survival (OS) from time of diagnosis of 7.6 months.ConclusionsWe demonstrate clinical efficacy of first-line osimertinib in the treatment of advanced NSCLC harbouring uncommon EGFR L861R and EGFR exon 18 deletion-insertion mutations. These results may be suggestive of the wider applicability of osimertinib in the treatment of uncommon EGFR mutant NSCLC.
| S-EPMC10938107 | biostudies-literature
Project description:Tyrosine kinase inhibitors (TKIs) represent the standard treatment for patients with non-small cell lung cancer (NSCLC) harboring epidermal growth factor receptor (EGFR) mutations. The duration of the response is, however, limited in time owing to the development of resistance mechanisms to both first- and second-generation agents such as MET oncogene amplification. This report describes the successful results obtained with the combination of the third-generation TKI osimertinib with the multitargeted TKI and MET inhibitor crizotinib in a patient with EGFR-mutant NSCLC with emerging MET amplification with a tolerable toxicity profile.
| S-EPMC8077408 | biostudies-literature
Project description:Background Kinase domain duplication of EGFR (EGFR-KDD) is a rare oncogenic driver alteration and serves as a potential therapeutic target. Its effect on EGFR–tyrosine kinase inhibitors (TKIs), especially the third-generation drug Osimertinib, and immune checkpoint inhibitors (ICIs) remains inconclusive. Case Presentation A 45-year old male with lung adenocarcinoma progressed with liver metastasis after receiving pemetrexed and cisplatin as adjuvant chemotherapy. Targeted next-generation sequencing (NGS) identified an EGFR-KDD in the resected left upper lung. Icotinib was used in the following treatment and the liver metastasis was found to shrink but the progression-free survival (PFS) only lasted for 4 months with the appearance of right hepatic metastasis. Meantime, the same EGFR-KDD was identified in the left hepatic re-biopsy. Afterward, the patient benefited from the third-line therapy of Osimertinib with a PFS as long as 21 months. Then he progressed with enlarged mediastinal lymph nodes, and targeted NGS consistently identified EGFR-KDD, as well as a new RELN p.G1774E mutation. Given the continually increasing tumor mutation burden (TMB, 3.4 mutation/Mb) and PD-L1 expression-based tumor proportion score (TPS, 1%), Nivolumab was used as the fourth-line salvage therapy, which lead to considerable efficacy, with decreased blood carcinoembryonic antigen (CEA), regressed mediastinal lymph nodes, and reduced liver metastases. Conclusions Our case provided direct evidence to support the role of Osimertinib in the treatment of EGFR-KDD, as well as added valuable insights into application of immune-based therapeutics in the specific subgroups bearing EGFR alteration(s).
| S-EPMC7773813 | biostudies-literature
Project description:Limited strategies are available at disease progression on osimertinib for patients with EGFR-mutant NSCLC. The emergence of the on-target EGFR C797S mutation has been described as one of the most common mechanisms of resistance. In addition, loss of the EGFR T790M mutation has been mainly investigated as a resistance phenomenon to second-line osimertinib exposure. Remarkably, by studying the molecular profile at progression, it has been reported that the presence of the EGFR-sensitizing mutation, concurrently with the T790M, and C797S resulted in resistance to the current available EGFR tyrosine kinase inhibitors. Here, we report the first clinical evidence of gefitinib efficacy at EGFR exon 19 deletion/C797S mutation/T790M loss-mediated resistance to first-line osimertinib. Our findings highlight that dynamic genetic monitoring is a crucial approach in the evolution of EGFR-mutant NSCLC to understand the acquired molecular mechanisms for driving the best treatment strategy.
| S-EPMC9926104 | biostudies-literature
Project description:IntroductionThe clinical efficacy of osimertinib for patients with lung adenocarcinoma harboring epidermal growth factor receptor (EGFR) exon 20 insertion mutations is unclear. Few case reports exist on the successful treatment of such tumors with osimertinib. We report a case wherein osimertinib administration had no effect in a patient with EGFR exon 20 insertion-positive lung adenocarcinoma.Patient concernsA 48-year-old never-smoking woman was referred to our hospital for chronic cough. Computed tomography (CT) and positron emission tomography-CT revealed a nodule in the right middle lobe, consolidation in the right upper lobe, multiple lymph node metastases, liver metastasis, and multiple bone metastases.DiagnosisOn the basis of further examination using transbronchial lung biopsy, the patient was diagnosed with cT1N3M1 stage IVB lung adenocarcinoma. An EGFR exon 20 insertion, without any additional mutations, was identified.InterventionsDaily oral administration of 80 mg osimertinib was initiated to treat the EGFR exon 20 insertion-positive lung adenocarcinoma.OutcomesAlthough the disease appeared to be stable 2.5 months after the administration of osimertinib, the tumor started to grow 3 months after administration, and carcinoembryonic antigen levels became higher than those before treatment. Thus, osimertinib was discontinued, and treatment with carboplatin as well as pemetrexed and bevacizumab was started, which the patient responded to.ConclusionEGFR exon 20 insertion mutations must be classified in more detail to assess the efficacy of EGFR tyrosine kinase inhibitors. Osimertinib doses that provide favorable therapeutic windows should be considered. Further clinical research is required to clarify the efficacy of osimertinib and other drugs for exon 20 insertion mutations.
| S-EPMC7572000 | biostudies-literature