A case of hyperprogressive disease following atezolizumab therapy for pulmonary pleomorphic carcinoma with epidermal growth factor receptor mutation

Oguri, Tomoyo; Sasada, Shinji; Seki, Syûzô; Murata, Saori; Tsuchiya, Yumi; Ishioka, Kota; Takahashi, Saeko; Seki, Reishi; Hirose, Shigemichi; Katayama, Ryohei; Nakamura, Morio

doi:10.1016/j.rmcr.2021.101405

Cited by 12 publications

(8 citation statements)

References 21 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of systemic progression after osimertinib, the second-line treatment would be chemoimmunotherapy in the current case. ICI monotherapy would be out of the question because hyperprogressive disease following ICI monotherapy for PPC harboring EGFR mutation has been reported [22]. The preferred chemoimmunotherapy regimen would be atezolizumab in combination with bevacizumab, carboplatin, and solvent-based paclitaxel, which has demonstrated significant efficacy on patients with NSCLC harboring EGFR mutation [23].…”

Section: Discussionmentioning

confidence: 99%

Pulmonary Pleomorphic Carcinoma Harboring EGFR Mutation Successfully Treated with Osimertinib: A Case Report

et al. 2022

View full text Add to dashboard Cite

Pulmonary pleomorphic carcinoma (PPC) is well-known for its aggressive nature that is usually resistant to platinum-based chemotherapy. On the other hand, the efficacy of an immune checkpoint inhibitor-based regimen in PPC has been elucidated. PPCs harboring epidermal growth factor receptor (EGFR) mutations are extremely rare, and the efficacy of EGFR-tyrosine kinase inhibitors in PPC is limited compared to their efficacy in EGFR-mutated adenocarcinoma. A 43-year-old female patient presenting with a lung mass with multiple brain metastases, carcinomatous pericarditis, and multiple bone metastases was referred to our department. Transbronchial biopsy confirmed the diagnosis of PPC harboring an EGFR mutation with exon 19 deletion. Subsequently, she was treated with osimertinib, a third-generation EGFR-tyrosine kinase inhibitor, which resulted in partial response with shrinkage of the primary lesion and brain metastases. This partial response remained durable for 11 months with an ongoing regimen. The current case suggests that osimertinib would show promising effects as a first-line treatment for PPCs harboring EGFR mutations, as well as a reasonable sequence of therapy followed by immune checkpoint inhibitor-based regimens.

show abstract

Section: Discussionmentioning

confidence: 99%

Pulmonary Pleomorphic Carcinoma Harboring EGFR Mutation Successfully Treated with Osimertinib: A Case Report

et al. 2022

View full text Add to dashboard Cite

show abstract

“…Although ICIs have been found to significantly prolong the survival of advanced NSCLC patients harboring wild-type EGFR, their benefits are limited in NSCLC patients with EGFR mutations (21,22), with some of these patients even developing hyper-progressive disease (HPD) in response to ICIs treatment (23). Some NSCLC patients with EGFR mutations, however, do have response to ICIs, but the characteristics of the potential beneficial population remain obscure.…”

Section: Discussionmentioning

confidence: 99%

Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint inhibitors

et al. 2022

View full text Add to dashboard Cite

BackgroundAlthough immune checkpoint inhibitors (ICIs) generally show poor therapeutic efficacy in patients with epidermal growth factor receptor (EGFR) mutations, certain research indicate that a small proportion of these patients do respond to ICIs. The present study sought to identify the features of patients with EGFR mutations who might benefit from ICIs from multiple studies and discussed the optimal treatment paradigm for advanced non-small cell lung cancer (NSCLC) patients with EGFR mutations.MethodsThe profiles of 114 advanced NSCLC patients with EGFR mutations who received ICIs treatment were retrospectively reviewed. EGFR subtypes, programmed cell death ligand 1 (PD-L1) expression, and clinical characteristics regarding their impact on the efficacy of ICIs were investigated.ResultsPatients with major EGFR mutations (L858R or 19Del) had a shorter progression-free survival (PFS) and a lower objective response rate (ORR) as compared to patients with rare (20ins or G719X) and other EGFR mutations. Although not statistically significant, median overall survival (OS) tended to be longer in patients with negative (<1%) PD-L1 expression than with positive (≥1%) PD-L1 expression (15.61 vs. 7.40 months, p = 0.138). Median PFS and OS were significantly shorter in heavily treated patients (prior lines of therapy ≥3 lines vs. <3 lines: mPFS, 1.80 vs. 2.50 months, p = 0.003; mOS, 6.70 vs. 14.00 months, p = 0.031). ORR was also lower in patients who had received ≥3 prior lines of therapy compared to in those <3 prior lines of therapy (0.00% vs. 21.67%, p = 0.002).ConclusionPatients with major EGFR mutations showed poorer responses to ICIs than those with rare EGFR mutations. EGFR-mutated patients with lower PD-L1 expression showed a trend towards a longer OS after receiving ICIs. ICIs should be administered as early as possible to previously treated EGFR-mutated NSCLC patients. ICI-based combined therapies may be a direction for treatment of these patient subtypes in the future.

show abstract

“…It was reported (24) that after receiving the first-line immunomonotherapy, an elderly patient with metastatic squamous cell lung cancer harboring both EGFR mutation and high PD-L1 expression presented with continuously aggravated conditions and died 6 months later. Additionally, Oguri T et al (25) reported that atezolizumab monotherapy led to immunotherapy-related hyperprogression in a patient with EGFR p.L858R-mutated pulmonary pleomorphic carcinoma. Similar to the above two cases, our case also involved high PD-L1 expression and EGFR p.L858R mutations with FOXP3 and M2 macrophages in the preoperative immune microenvironment, which was associated with the development of hyper progressive diseases (HPDs).…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, Oguri T et al. ( 25 ) reported that atezolizumab monotherapy led to immunotherapy-related hyperprogression in a patient with EGFR p.L858R-mutated pulmonary pleomorphic carcinoma. Similar to the above two cases, our case also involved high PD-L1 expression and EGFR p.L858R mutations with FOXP3 and M2 macrophages in the preoperative immune microenvironment, which was associated with the development of hyper progressive diseases (HPDs).…”

Section: Discussionmentioning

confidence: 99%

EGFR mutations and high PD-L1 expression of lung squamous cell carcinoma patients achieving pCR following neoadjuvant immuno-chemotherapy: Case report

Shi²,

Fu³

et al. 2022

Front. Oncol.

View full text Add to dashboard Cite

The treatment of lung cancer has fully entered the era of immunotherapy, which has significantly elevated the survival rate of patients with advanced non-small cell lung cancer (NSCLC), thus shedding light on resectable NSCLC. Previous clinical trial data suggested that neoadjuvant immuno-chemotherapy obtained a significant objective response rate (ORR) and disease control rate (DCR). Here, a case that achieved an excellent outcome following neoadjuvant immuno-chemotherapy was reported. The patient admitted to our hospital was 58 years old, female, with a rare case of stage IB lung squamous cell carcinoma (LUSC) harboring both epidermal growth factor receptor (EGFR) p.L858R mutations and high expression of programmed death ligand-1 (PD-L1) (tumor proportion score (TPS)=80%). Her tumor substantially shrunk following two cycles of neoadjuvant immuno-chemotherapy. The patient successively received single-port right upper thoracoscopic lobectomy + mediastinal lymph node dissection, which attained pathologic complete response (pCR). Additionally, the patient had grade 2 myelosuppression during the two cycles, which was treated with polyethylene glycol recombinant human granulocyte colony-stimulating factor (rhG-CSF). The patient was discharged uneventfully without any procedure-related complications. Two courses of adjuvant immuno-chemotherapy were administered postoperatively, leaving the patient in good physical condition at the 5-month follow-up visit. This case provided evidence for the feasibility and effectiveness of neoadjuvant immuno-chemotherapy in treating early-stage LUSC with EGFR mutations and high expression of PD-L1. However, randomized and multi-center controlled trials are required to validate the findings.

show abstract

A case of hyperprogressive disease following atezolizumab therapy for pulmonary pleomorphic carcinoma with epidermal growth factor receptor mutation

Cited by 12 publications

References 21 publications

Pulmonary Pleomorphic Carcinoma Harboring EGFR Mutation Successfully Treated with Osimertinib: A Case Report

Pulmonary Pleomorphic Carcinoma Harboring EGFR Mutation Successfully Treated with Osimertinib: A Case Report

Features of patients with advanced EGFR-mutated non-small cell lung cancer benefiting from immune checkpoint inhibitors

EGFR mutations and high PD-L1 expression of lung squamous cell carcinoma patients achieving pCR following neoadjuvant immuno-chemotherapy: Case report

Contact Info

Product

Resources

About