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Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry
Open accessAbstract
Background Anti-PD1/PD-L1 directed immune checkpoint inhibitors (ICI) are widely used to treat patients with advanced non-small-cell lung cancer (NSCLC). The activity of ICI across NSCLC harboring oncogenic alterations is poorly characterized. The aim of our study was to address the efficacy of ICI in the context of oncogenic addiction. Patients and methods We conducted a retrospective study for patients receiving ICI monotherapy for advanced NSCLC with at least one oncogenic driver alteration. Anonymized data were evaluated for clinicopathologic characteristics and outcomes for ICI therapy: best response (RECIST 1.1), progression-free survival (PFS), and overall survival (OS) from ICI initiation. The primary end point was PFS under ICI. Secondary end points were best response (RECIST 1.1) and OS from ICI initiation. Results We studied 551 patients treated in 24 centers from 10 countries. The molecular alterations involved KRAS (n = 271), EGFR (n = 125), BRAF (n = 43), MET (n = 36), HER2 (n = 29), ALK (n = 23), RET (n = 16), ROS1 (n = 7), and multiple drivers (n = 1). Median age was 60 years, gender ratio was 1 : 1, never/former/current smokers were 28%/51%/21%, respectively, and the majority of tumors were adenocarcinoma. The objective response rate by driver alteration was: KRAS = 26%, BRAF = 24%, ROS1 = 17%, MET = 16%, EGFR = 12%, HER2 = 7%, RET = 6%, and ALK = 0%. In the entire cohort, median PFS was 2.8 months, OS 13.3 months, and the best response rate 19%. In a subgroup analysis, median PFS (in months) was 2.1 for EGFR, 3.2 for KRAS, 2.5 for ALK, 3.1 for BRAF, 2.5 for HER2, 2.1 for RET, and 3.4 for MET. In certain subgroups, PFS was positively associated with PD-L1 expression (KRAS, EGFR) and with smoking status (BRAF, HER2). Conclusions : ICI induced regression in some tumors with actionable driver alterations, but clinical activity was lower compared with the KRAS group and the lack of response in the ALK group was notable. Patients with actionable tumor alterations should receive targeted therapies and chemotherapy before considering immunotherapy as a single agent.
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Cites
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STK11/LKB1 Mutations and PD-1 Inhibitor Resistance in KRAS -Mutant Lung Adenocarcinoma
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BackgroundSelf-citationCheckpoint inhibitors in metastatic EGFR-mutated non–small cell lung cancer-a meta-analysis
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Trastuzumab Deruxtecan in HER2 -Mutant Non–Small-Cell Lung Cancer
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Self-citationOvercoming therapy resistance in EGFR-mutant lung cancer
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Metadata
- Authors
- Mazieres, J., Drilon, A., Lusque, A., Mhanna, L., Cortot, A. B., Mezquita, L., Thai, A. A., Mascaux, C., Couraud, S., Veillon, R., Van den Heuvel, M., Neal, J., Peled, N., Früh, M., Ng, T. L., Gounant, V., Popat, S., Diebold, J., Sabari, J., Zhu, V. W., Rothschild, S. I., Bironzo, P., Martinez-Marti, A., Curioni-Fontecedro, A., Rosell, R., Lattuca-Truc, M., Wiesweg, M., Besse, B., Solomon, B., Barlesi, F., Schouten, R. D., Wakelee, H., Camidge, D. R., Zalcman, G., Novello, S., Ou, S. I., Milia, J., & Gautschi, O.
- Venue
- Annals of Oncology
- Publisher
- Elsevier BV
- Published
- 2019-08
- Volume
- 30
- Issue
- 8
- Pages
- 1321-1328
- ISSN
- 0923-7534 (ISSN-L)
- OpenAlex
- W2946166987
- Cited by
- 1,354
- References
- 12
- FWCI
- 54.87
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Mazieres, J., Drilon, A., Lusque, A., Mhanna, L., Cortot, A. B., Mezquita, L., Thai, A. A., Mascaux, C., Couraud, S., Veillon, R., Van den Heuvel, M., Neal, J., Peled, N., Früh, M., Ng, T. L., Gounant, V., Popat, S., Diebold, J., Sabari, J., . . . Gautschi, O. (2019). Immune checkpoint inhibitors for patients with advanced lung cancer and oncogenic driver alterations: results from the IMMUNOTARGET registry. Annals of Oncology. https://doi.org/10.1093/annonc/mdz167
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