Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

Bearz, Alessandra; Talamini, Renato; Rossoni, G.; Santo, Antonio; Pangher, V. De; Fasola, Gianpiero; Rosetti, Francesco; Favaretto, Adolfo; Gregorc, Vanesa; Berretta, Massimiliano; Santarossa, Sandra; Berto, Eleonora; Tirelli, Umberto

doi:10.1186/1756-0500-5-482

Cited by 41 publications

(36 citation statements)

References 26 publications

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“…Patients with a TFS of ≥3 months also exhibited a longer PFS2 compared to those with a TFS of <3 months. Such results are similar to those reported by previous studies on MPM patients (4,6). However, the cut-off value of PFS1 in this study was shorter compared to that in the study of Ceresoli et al (4) (10 vs. 12 months, respectively).…”

Section: Discussionsupporting

confidence: 90%

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Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer

Zhuo

Bai

Wang

et al. 2014

Molecular and Clinical Oncology

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Abstract. Rechallenge chemotherapy with pemetrexed was shown to be efficient in malignant pleural mesothelioma; however, its role in non-small-cell lung cancer (NSCLC) has not been investigated. In this study, we retrospectively enrolled 31 patients with non-squamous NSCLC who had achieved disease control with initial pemetrexed treatment, followed by rechallenge with pemetrexed-based chemotherapy (PBC) upon disease progression. After the rechallenge, 5 patients (16.1%) achieved partial remission (PR), 17 (54.8%) achieved stable disease (SD) and 9 (29.1%) experienced progressive disease. The treatment was generally well tolerated, with a low rate of toxicity. The median progression-free survival (PFS) was 3.8 months with the rechallenge. Patients with a PFS of ≥10 months with initial PBC exhibited longer PFS and overall survival (OS) with the rechallenge compared to those with a PFS of <10 months with initial PBC (PFS: 6.2±0.33 vs. 3.1±0.26 months, respectively; P= 0.011; and OS, 19.8±3.2 vs. 9.2±1.1 months, respectively; P=0.005). The time from the termination of initial PBC to disease progression was also associated with survival after the rechallenge. However, the response to initial PBC (PR vs. SD) did not affect PFS after the rechallenge. No significant differences were observed in thymidylate synthase expression, echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase gene fusion, or epithelial growth factor receptor mutation status between pemetrexed-sensitive and pemetrexed-resistant patients. Our results demonstrated that rechallenge with PBC was well tolerated and survival after the rechallenge was associated with survival during initial PBC. Therefore, patients with a PFS of ≥10 months or time-to-disease progression ≥3 months may be considered as candidates for pemetrexed rechallenge.

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Section: Discussionsupporting

confidence: 90%

“…It was recently demonstrated that PBC may be used as rechallenge treatment in MPM patients who achieve a PFS ≥12 months with first-line PBC (4)(5)(6). We have also noticed in clinical practice that certain patients with non-squamous NSCLC benefited from rechallenge with PBC as second-or further-line treatment.…”

Section: Introductionmentioning

confidence: 87%

Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer

Zhuo

Bai

Wang

et al. 2014

Molecular and Clinical Oncology

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“…Generally, it is suggested that retreatment should be considered in patients achieving an at least 12-month disease control with first-line therapy [16,18]. Our data seem to support this idea, and, according to our experience, we feel that second-and third-line treatments are inappropriate in patients not responding to firstline therapy.…”

Section: Discussionsupporting

confidence: 75%

“…In everyday clinical practice, a second-line CT is offered at progression. Median survival varies between 10.5 and 13.6 months for re-challenge with a pemetrexed-based therapy, and between 6.2 and 20.8 months in patients treated with other CTs [11,16,18].…”

Section: Discussionmentioning

confidence: 99%

Clinical Features and Treatment Outcome of Malignant Pleural Mesothelioma

Filiberti

Taveggia²,

Grosso

et al. 2017

Oncol Res Treat

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Background: Malignant pleural mesothelioma is a problematic condition due to poor prognosis and difficulties in management. We evaluated the treatment and outcome of 378 mesothelioma patients referred to 6 Italian Oncology Departments. Methods: Demographic and clinical data were collected. Treatment was assessed in terms of chemotherapy (line of treatment, pemetrexed-based regimen, other therapies), surgery, and radiotherapy. Response to therapy, progression-free survival, and overall survival were evaluated. Results: 36 and 342 patients received best supportive care and active treatment, respectively; 86 patients underwent surgery, and 26 received trimodal therapy. Disease control after first-line chemotherapy was achieved in 74.2% of patients (75.7% in patients treated with pemetrexed combined with other drugs and 69% with pemetrexed as monotherapy). The disease control rate was 82.6% in pemetrexed re-challenged individuals. Median survival time was 11.6 months with supportive care, 16.2 months with chemotherapy only, 32.4 months with surgery plus chemotherapy, and 47.2 months with trimodal therapy. A more favorable prognosis was observed in responders to first-line therapy who were then actively treated with second-line (24.8 vs. 11.8 months in non-responders, p < 0.001) and third-line chemotherapy (28.9 vs. 17.8 months in non-responders, p = 0.005). Conclusion: Mesothelioma patients benefited from chemotherapy alone only when retreated in the second line after response to first-line therapy.

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“…Bearz et al selected 30 patients from 7 Italian centers in a retrospective study (9). Mesothelioma histology was epithelioid in 28 patients and mixed in 2, 1 patient had an extra pleural localization in the tunica vaginalis.…”

Section: Rechallenge With Pemetrexedmentioning

confidence: 99%

Medical treatment of malignant pleural mesothelioma relapses

et al. 2018

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Pattern of mesothelioma relapsesPatients with resectable mesothelioma can benefit from multimodality treatments that can include induction chemotherapy plus extrapleural pneumonectomy and then post-operative radiotherapy or pleurectomy decortication followed by chemotherapy. The first approach has significantly higher perioperative mortality and complications (1). Patterns of relapse are different between the two techniques. After pleurectomy decortication, local relapses are more frequent including progressions in homolateral chest and pericardium. After extrapleural pneumonectomy, progressions in distant sites were more common including contralateral lung/pleural, lymph nodes and peritoneum (2). However, extrapleural pneumonectomy also local recurrences have been reported with or without concomitant distant metastases in 31% and 46% of completely resected tumors, respectively (3). In the MARS trial, that compare extrapleural pneumonectomy with less invasive approaches, the progression free survival (PFS) was 7.6 and 9 months, respectively (4).Unresectable patients benefit from chemotherapy, being the standard of care the combination of pemetrexed and cisplatin. In a phase III trial, 226 and 222 chemotherapy naïve mesothelioma patients were randomly assigned to receive cisplatin with or without pemetrexed, respectively (5). The combination increased survival compared with cisplatin alone: 12.1 vs. 9.3 months (P=0.002). Similarly, time to progression was longer in the combination arm: 5.7 vs. 3.9 months (P=0.001).The French Cooperative Thoracic Intergroup conducted a phase III trial to compare the first line treatment with cisplatin-pemetrexed with or without the addiction of bevacizumab (6). Two hundred and twenty-three and 225 patients were randomly assigned to receive treatment with or without bevacizumab, respectively. The group treated with bevacizumab obtained an increased overall survival (OS) compared to the control arm (median OS 18.8 vs. 16.1 months, respectively; hazard ratio 0.77; P=0.0167). Similarly, an increase of PFS was observed with bevacizumab (median 9.2 vs. 7.3 months; P<0.0001). A higher rate of bevacizumab related side effects were observed in the experimental arm:

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Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

Cited by 41 publications

References 26 publications

Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer

Rechallenge with pemetrexed-based chemotherapy improves the survival of patients with advanced non-squamous non-small-cell lung cancer

Clinical Features and Treatment Outcome of Malignant Pleural Mesothelioma

Medical treatment of malignant pleural mesothelioma relapses

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