Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

Knetki-Wróblewska, Magdalena; Wojas‐Krawczyk, Kamila; Kowalski, Dariusz M.; Krzakowski, Maciej

doi:10.3390/jcm11061630

Cited by 4 publications

(4 citation statements)

References 34 publications

(66 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In a separate case series, Rodriguez et al. observed that patients with RET -arranged lung cancers and high PD-L1 expression exhibited positive responses to immunotherapy ( 32 ). Furthermore, Baby, S. et al.…”

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report

Dai,

Wang,

Xia

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

Neoadjuvant chemoimmunotherapy has demonstrated significant benefit for resectable non-small-cell lung cancer (NSCLC) excluding known EGFR/ALK genetic alterations. Recent evidence has shown that neoadjuvant chemoimmunotherapy could be clinically valuable in resectable localized driver gene-mutant NSCLC, though the data still lack robust support, especially for rare oncogenic mutations. Here, we report a patient with stage IIIA lung adenocarcinoma with a RET fusion gene and high expression of PD-L1 who underwent neoadjuvant chemoimmunotherapy and successfully attained a pathologic complete response. The patient has survived for 12 months with no recurrence or metastases after surgery. Our case suggests that this treatment strategy may be an alternative therapeutic option for resectable RET fusion-positive NSCLC patients.

show abstract

Section: Discussionmentioning

confidence: 99%

Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report

Dai,

Wang,

Xia

et al. 2024

Front. Immunol.

View full text Add to dashboard Cite

show abstract

“…Selpercatinib, similar to other molecular-targeted therapies, had sufficient systemic effects (12,13), including brain metastases (14). In general, first-line treatment for gene mutation-positive lung adenocarcinoma is the corresponding molecular-targeted drug; however, this case suggests that the order of drugs used may be important when aiming for the longest overall survival by sequence therapy (15). In a phase 3 study of selpercatinib for RET-positive lung cancer, the efficacy of molecular-targeted drugs, in addition to the therapeutic effects Pathologic findings from the first diagnostic cell block showed adenocarcinoma in the presence of many lymphocytes (A, B, H&E staining, original magnification × 400).…”

Section: Discussionmentioning

confidence: 99%

RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report

et al. 2022

View full text Add to dashboard Cite

Personalized medicine using molecular-targeted drugs to achieve better therapeutic response and long-term prognosis is common practice for lung cancer treatment. However, in cases before gene batch tests were available, medical treatment continued without the detection of rare mutations. We report a sixty-seven-old year man diagnosed with adenocarcinoma T1cN3M1a, stage IVA. Initial screening performed 7 years earlier using EGFR mutation and ALK immunohistochemical tests were negative. Although first-line cytotoxic combination chemotherapy was remarkably effective, a gradual regression of the primary lesion was noted. After a recent bronchoscopic re-biopsy, RET fusion was detected by gene panel test. In addition, we were able to confirm RET from FFPE specimens obtained from 7-year-old pleural effusion cell blocks. Subsequent administration of the molecular-targeted drug selpercatinib, was highly effective for the primary lesion and all metastatic lesions including brain metastases. We describe a case of RET fusion-positive lung cancer where molecular targeted therapy and cytotoxic drug showed a drastic response and long-term therapy was well maintained. Next generation sequencing was able to correctly diagnose RET fusion mutation using re-biopsy specimen after going undiagnosed for 7 years.

show abstract

“…Lung tumors with RET fusions usually appear in patients without a smoking history. Such tumors tend to have a low tumor mutation burden (TMB) and are poorly infiltrated by immunological cells, which in effect present low expression of PD-L1, and hence weak response to ICIs [ 63 ].…”

Section: Immunotherapy In Tumors With Genetic Changes Of Ret Genementioning

confidence: 99%

RET Proto-Oncogene—Not Such an Obvious Starting Point in Cancer Therapy

Kucharczyk

Krawczyk

Kowalski³

et al. 2022

Cancers

Self Cite

View full text Add to dashboard Cite

Mutations and fusions of RET (rearranged during transfection) gene are detected in a few common types of tumors including thyroid or non-small cells lung cancers. Multiple kinase inhibitors (MKIs) do not show spectacular effectiveness in patients with RET-altered tumors. Hence, recently, two novel RET-specific inhibitors were registered in the US and in Europe. Selpercatinib and pralsetinib showed high efficacy in clinical trials, with fewer adverse effects, in comparison to previously used MKIs. However, the effectiveness of these new drugs may be reduced by the emergence of resistance mutations in RET gene and activation of different activating signaling pathways. This review presents the function of the normal RET receptor, types of molecular disturbances of the RET gene in patients with various cancers, methods of detecting these abnormalities, and the effectiveness of modern anticancer therapies (ranging from immunotherapies, through MKIs, to RET-specific inhibitors).

show abstract

Non-Small-Cell Lung Cancer Patients with Coexistence of High PD-L1 Expression and RET Fusion—Which Path Should We Follow? Case Reports and Literature Review

Cited by 4 publications

References 34 publications

Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report

Neoadjuvant chemoimmunotherapy achieved a pathologic complete response in stage IIIA lung adenocarcinoma harboring RET fusion: a case report

RET fusion mutation detected by re-biopsy 7 years after initial cytotoxic chemotherapy: A case report

RET Proto-Oncogene—Not Such an Obvious Starting Point in Cancer Therapy

Contact Info

Product

Resources

About