Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status. Methods: In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis. Results: A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 – 1.86, P = 0.54). Heterogeneity was significant (I2 = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 – 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I2 = 85 %; P = 0.009). Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.

Musacchio, L., Valsecchi, A. A., Salutari, V., Valabrega, G., Camarda, F., Tuninetti, V., Giannone, G., Bartoletti, M., Marchetti, C., Pignata, S., Fagotti, A., Scambia, G., Di Maio, M., Lorusso, D., MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis, <<CANCER TREATMENT REVIEWS>>, 2022; 110 (102458): N/A-N/A. [doi:10.1016/j.ctrv.2022.102458]

MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis

Salutari, V.;Camarda, F.;Marchetti, C.;Fagotti, A.;Scambia, G.;Lorusso, D.
2022

Abstract

Background: Low grade serous carcinoma of the ovary and peritoneum (LGSC) is characterized by low response rates to chemotherapy and by MAPK pathway alterations. Phase II/III clinical trials tested different MEK inhibitors (MEKis) in this complex malignancy, with heterogenous results. Purpose of this systematic review and meta-analysis is to define activity and efficacy of these agents and explore differences in clinical outcomes related to RAS/RAF mutational status. Methods: In March 2022, we searched Pubmed, Web of Science, Scopus, and the major conference proceedings (ASCO, ESMO) for randomized and non-randomized clinical trials evaluating MEKi as single agent in recurrent LGSC. The screening was performed independently by two reviewers. Objective response rate (ORR) and progression-free survival (PFS) data were extracted, and RevMan 5.3 software was used for statistical analysis. Results: A total of 4 clinical trials involving 648 patients were included. In the intention-to-treat population, use of a MEK inhibitor was not associated with a significant improvement in PFS, with a pooled Hazard Ratio equal to 0.75 (95 % CI: 0.30 – 1.86, P = 0.54). Heterogeneity was significant (I2 = 92 %; P = 0.0004). In the overall study population, the pooled odds ratio of ORR for MEKis compared to control treatment was 2.61 (95 % CI: 0.65 – 10.54, P = 0.18). Specifically, ORR was 20.12 % in patients treated with MEKis compared to 9.09 % in women receiving standard treatment. Heterogeneity was significant (I2 = 85 %; P = 0.009). Conclusions: Although no statistically significant improvement in PFS was demonstrated, the available data show clear signals of activity, at least for some MEKis.
Inglese
Musacchio, L., Valsecchi, A. A., Salutari, V., Valabrega, G., Camarda, F., Tuninetti, V., Giannone, G., Bartoletti, M., Marchetti, C., Pignata, S., Fagotti, A., Scambia, G., Di Maio, M., Lorusso, D., MEK inhibitor as single agent in low grade serous ovarian and peritoneal cancer: a systematic review and meta-analysis, <<CANCER TREATMENT REVIEWS>>, 2022; 110 (102458): N/A-N/A. [doi:10.1016/j.ctrv.2022.102458]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/10807/219720
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