Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

Guisier, Florian; Descourt, R.; Babey, H.; Huchot, É.; Falchero, L.; Veillon, Rémi; Cortot, AB.; Tissot, Claire; Chouaïd, C.; Decroisette, C.

doi:10.1016/j.cllc.2022.09.002

Cited by 6 publications

(2 citation statements)

References 15 publications

(17 reference statements)

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“…These results revealed that MET inhibitors at least partially inhibit PD-1/PD-L1 signaling. However, despite high PD-L1 expression in MET ex14 NSCLC, the efficacy of PD-1/PD-L1 inhibitors seems lower than expected, with reported overall response rates ranging between 16% and 43% [ 28 , 45 , 46 ]. On the basis of the demonstration of the dynamic nature of PD-L1 expression with MET inhibitors demonstrated in our study, the timing and sequence of targeted and immunotherapy warrant further investigation.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneous Expression of PD-L1, B7x, B7-H3, and HHLA2 in Pulmonary Sarcomatoid Carcinoma and the Related Regulatory Signaling Pathways

Wang

Daylan

Deng

et al. 2023

Cancers

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Immunotherapy has transformed lung cancer management, but PSC remains an aggressive subtype with a poor prognosis. This study investigates the differential expression of PD-L1 and alternative immune checkpoints (ICs; B7x, B7-H3, and HHLA2), and genetic alterations in PSCs. Tumor specimens of 41 PSC patients were evaluated. PD-L1, B7x, B7-H3, and HHLA2 were positive in 75.0%, 67.6%, 73.0%, and 91.9% of tumors, respectively. PD-L1 expression was significantly higher in the epithelial compared to the sarcomatoid component (median TPS: 50% vs. 0%, p = 0.010). Expression of PD-L1 in both components was only seen in 32.1% of patients. However, at least one IC was expressed in 92.9% of epithelial and 100% of sarcomatoid components. Furthermore, METex14 was detected in 19.5% of patients and was associated with a higher sarcomatoid percentage. Our preclinical studies revealed that METex14 induced PD-L1 expression via MAPK or PI3K/Akt pathways, and MET inhibitors decreased PD-L1 expression. Our findings demonstrate distinct expressions of ICs in PSC subcomponents. Thus, combination IC inhibition as a therapeutic strategy in PSC warrants further exploration. A high percentage of METex14 in PSC and its role in regulating PD-L1 expression reveal different therapeutic targets in this aggressive NSCLC subtype.

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Section: Discussionmentioning

confidence: 99%

Heterogeneous Expression of PD-L1, B7x, B7-H3, and HHLA2 in Pulmonary Sarcomatoid Carcinoma and the Related Regulatory Signaling Pathways

Wang

Daylan

Deng

et al. 2023

Cancers

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“…These observational data suggest that cancers with MET alterations could potentially benefit from treatments targeting immune checkpoint molecules (Immune Checkpoint Inhibitors, ICIs). This was assessed in a retrospective study in which stage IV NSCLC MET exon 14 skipping patients with >50% PD-L1 expression treated as first-line therapy with Pembrolizumab showed an improved therapeutic outcome [ 95 ].…”

Section: Inhibition Of Met Signaling To Modulate Cancer Immune Tolerancementioning

confidence: 99%

MET Oncogene Targeting for Cancer Immunotherapy

Lombardi,

Sangiolo,

Vigna

2024

IJMS

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The MET receptor is one of the main drivers of ‘invasive growth’, a multifaceted biological response essential during embryonic development and tissue repair that is usurped by cancer cells to induce and sustain the malignant phenotype. MET stands out as one of the most important oncogenes activated in cancer and its inhibition has been explored since the initial era of cancer-targeted therapy. Different approaches have been developed to hamper MET signaling and/or reduce MET (over)expression as a hallmark of transformation. Considering the great interest gained by cancer immunotherapy, this review evaluates the opportunity of targeting MET within therapeutic approaches based on the exploitation of immune functions, either in those cases where MET impairment is crucial to induce an effective response (i.e., when MET is the driver of the malignancy), or when blocking MET represents a way for potentiating the treatment (i.e., when MET is an adjuvant of tumor fitness).

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Pembrolizumab

2023

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Brief Report: First-line Pembrolizumab in Metastatic Non-Small Cell Lung Cancer Habouring MET Exon 14 Skipping Mutation and PD-L1 ≥50% (GFPC 01-20 Study)

Cited by 6 publications

References 15 publications

Heterogeneous Expression of PD-L1, B7x, B7-H3, and HHLA2 in Pulmonary Sarcomatoid Carcinoma and the Related Regulatory Signaling Pathways

Heterogeneous Expression of PD-L1, B7x, B7-H3, and HHLA2 in Pulmonary Sarcomatoid Carcinoma and the Related Regulatory Signaling Pathways

MET Oncogene Targeting for Cancer Immunotherapy

Pembrolizumab

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