A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma

Petrelli, Fausto; Ardito, Raffaele; Conti, Bárbara; Coinu, Andrea; Cabiddu, Mary; Ghilardi, Mara; Borgonovo, Karen; Barni, Sandro; Ghidini, Antonio

doi:10.1016/j.rmed.2018.06.026

Cited by 22 publications

(14 citation statements)

References 58 publications

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“…Our median OS reached 11.1 months, numerically higher than that reported in large meta-analyses (about 8 months). 18 In our trial, pts undergoing subsequent treatments did not live longer than those who did not and the same applied for pts having received lurbinectedin after immunotherapy. We may thus assume that neither further therapy nor previous immunotherapy influenced OS, which came close to the upper limits of any published OS so far and is only challenged by recently presented PROMISEmeso trial data.…”

Section: Discussionmentioning

confidence: 57%

“…4 These figures agree with older studies where PFS did not exceed 3 months in pts pretreated with pemetrexed, 5,6 while a recent meta-analysis revealed that no relevant improvement in second-and subsequent-line mesothelioma treatment had occurred over the 2005e2017 period. 18 While cross-trial comparison is hazardous, our PFS and control duration data seem promising compared with published data.…”

Section: Discussionmentioning

confidence: 63%

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Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

et al. 2020

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Background: Systemic second-and third-line therapies for malignant pleural mesothelioma (MPM) result in a median progression-free survival (mPFS) of <2 months and median overall survival (mOS) of 6e9 months. Lurbinectedin binds to the DNA of the regulatory region while inhibiting tumour-associated macrophage transcription. In early trials, encouraging outcomes occurred in patients (pts) with MPM treated with lurbinectedin. We aimed to generate lurbinectedin efficacy and safety data among pts with progressive MPM. Patients and methods: Pts with progressing MPM treated with first-line platinum-pemetrexed chemotherapy with or without immunotherapy received lurbinectedin monotherapy. Treatment was given intravenously at 3.2 mg/m 2 dose every 3 weeks until progression or unacceptable toxicity. Using Simon's two-stage design, the primary endpoint, progression-free survival (PFS) at 12 weeks (PFS 12wks ), was met if achieved by !21 pts (p0 35% versus p1 !55%). Results: Forty-two pts from nine centres across Switzerland and Italy were recruited. Histology was epithelioid in 33 cases, sarcomatoid in 5, and biphasic in 4. Overall 10/42 (23.8%) underwent prior immunotherapy and 14/42 (33.3%) had progressed 6 months after first-line chemotherapy. At data cut-off PFS 12wks was met by 22/42 pts (52.4%; 90% confidence interval (CI): 38.7% to 63.5%; P ¼ 0.015) with an mPFS of 4.1 months and mOS of 11.1 months. The best response was complete and partial remission observed in one patient each and stable disease in 20 pts. The duration of disease control was 6.6 months (95% CI: 5.2e7.4). No significant difference in PFS 12wks, mPFS, and mOS was recorded in epithelioid versus non-epithelioid cases and pts with prior immunotherapy versus those without. Similar mPFS but shorter mOS were observed among pts who progressed within 6 months after first-line chemotherapy. Lurbinectedin-related grade 3e4 toxicity was seen in 21 pts, mostly being neutropenia (23.8%) and fatigue (16.7%). Conclusions: The primary efficacy endpoint was reached with acceptable toxicity. Lurbinectedin showed promising activity regardless of histology, prior immunotherapy, or outcome on prior treatment. ClinicalTrials.gov Identifier: NCT03213301

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Section: Discussionmentioning

confidence: 57%

Section: Discussionmentioning

confidence: 63%

Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

et al. 2020

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“…The first-line chemotherapy regimen of MPM based on cisplatin plus pemetrexed can extend the median overall survival of MPM patients to 16.1 months (28). One of the main reasons for tumor progression after chemotherapy is the resistance of tumor cells to cisplatin (29). Therefore, to elucidate the mechanisms of resistance of MPM cells to cisplatin can benefit the treatment outcome of patients.…”

Section: Discussionmentioning

confidence: 99%

Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair

Chen

et al. 2021

Ann Transl Med

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Background: Malignant pleural mesothelioma (MPM) chemoresistance remains a challenge to oncologists.In our previous study, we demonstrated that the aberrant expression of metastasis-associated gene 1 (MTA1) is associated with carcinogenesis and metastasis in MPM. The aim of the present study was to investigate the mechanism of MTA1 and chemo-resistance in MPM. Methods: Western blotting and real-time polymerase chain reaction were used to analyze the protein and mRNA levels. A stable clone with a knockdown of MTA1 was generated with shRNA via lentivirus technology in MPM cell lines. Cell Counting Kit-8 assay and crystal violet assay were used to measure cell viability. Immunochemical staining was employed to detect MTA1 expression in MPM tissues. The cell cycle of MPM cells was determined by phosphohistone H3 staining and flow cytometric analysis. Results: The MTA1 protein was upregulated and enhanced cisplatin resistance in MPM. Cisplatin stabilized the expression of the MTA1 protein by inhibiting its ubiquitination, and MTA1 enhanced G2/ M cell cycle delay and regulated and protected the tumor genome from chemotherapeutic drugs via participating in the phosphorylation of the ataxia telangiectasia mutated and rad3 related-checkpoint kinase 1 (ATR-Chk1) pathway. Conclusions: These data suggest that MTA1 enhances cisplatin resistance by ATR-Chk1-mediated DNA damage repairment and cisplatin stabilizes MTA1 expression via affecting on the ubiquitination pathway of MTA1 in MPM. Our findings indicate that MTA1 could serve as a novel therapeutic target to overcome chemoresistance in MPM.

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“…MM has continued to defy trials of novel therapies and remains an incalcitrant and highly mortal cancer. 123,124 However, research during the last few years has shed significant new knowledge into the genetics and pathobiology of MM. 82,125,126 These advances have greatly energized the field and generated enthusiasm for clinical trials in MM involving novel agents and therapeutic strategies, including immunotherapies.…”

Section: Consensus Recommendationsmentioning

confidence: 99%

Pathologic Considerations and Standardization in Mesothelioma Clinical Trials

Tsao

Carbone

Galateau-Salle

et al. 2019

Journal of Thoracic Oncology

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A systematic review and meta-analysis of second-line therapies for treatment of mesothelioma

Cited by 22 publications

References 58 publications

Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

Lurbinectedin as second- or third-line palliative therapy in malignant pleural mesothelioma: an international, multi-centre, single-arm, phase II trial (SAKK 17/16)

Metastasis-associated gene 1 (MTA1) enhances cisplatin resistance of malignant pleural mesothelioma by ATR-Chk1-mediated DNA repair

Pathologic Considerations and Standardization in Mesothelioma Clinical Trials

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