Trimodality therapy—using mesothelioma chemotherapy, surgery, and hemithoracic RT—has been used in patients with MPM. Median survival of up to 20 to 29 months has been reported for patients who complete trimodality therapy. Nodal status and response to chemotherapy can affect survival. In patients who do not receive induction chemotherapy before EPP, postoperative sequential chemotherapy with hemithoracic RT is recommended. Intraoperative adjuvant therapies—such as hyperthermic pleural lavage, photodynamic therapy, or heated chemotherapy—have also been studied.
Mesothelioma chemotherapy is recommended either alone for medically inoperable patients with MPM or as part of a multimodality regimen for patients with medically operable MPM (see Treatment and Principles of Chemotherapy in the NCCN Guidelines for Malignant Pleural Mesothelioma). Patients with medically operable stage I to III MPM (epithelial histology) can receive chemotherapy either before or after surgery. Chemotherapy alone is recommended for patients with medically inoperable stages I to IV MPM, those who refuse surgery, and those with sarcomatoid or mixed histology. Pemetrexed-based chemotherapy can also be used for malignant peritoneal mesothelioma, pericardial mesothelioma, and tunica vaginalis testis mesothelioma.
A combined first-line regimen using cisplatin/pemetrexed (category 1) is recommended for MPM and is currently the only regimen approved by the FDA. A phase 3 randomized trial assessed cisplatin/pemetrexed versus cisplatin alone in patients who were not candidates for surgery; the combined regimen increased survival by 2.8 months when compared with cisplatin alone (12.1 vs. 9.3 months, P=.02). Based on this trial and the FDA approval, the NCCN Panel recommends cisplatin/pemetrexed (category 1) for patients with MPM.
A multicenter phase 3 randomized trial (IFCT-GFPC-0701 MAPS) compared adding bevacizumab to cisplatin/pemetrexed (with maintenance bevacizumab) versus cisplatin/pemetrexed alone for patients with unresectable MPM and PS 0 to 2 who did not have bleeding or thrombosis. Overall survival was increased in the bevacizumab plus chemotherapy arm by 2.7 months when compared with chemotherapy alone (18.8 vs. 16.1 months; HR = 0.77; P = .0167). Grade 3 to 4 adverse events were reported in 71% (158/222) of patients receiving the bevacizumab regimen when compared with 62% (139/224) of those receiving cisplatin/pemetrexed alone. More grade 3 or higher hypertension (23% vs. 0%), grade 3 proteinuria (3.1% vs. 0%), and grade 3-4 thrombotic events (6% vs. 1%) were observed in patients receiving the triplet arm. The NCCN Panel recommends (category 1) bevacizumab, cisplatin, and pemetrexed followed by maintenance bevacizumab for bevacizumab-eligible patients with unresectable MPM based on this trial (see Principles of Mesothelioma Chemotherapy in the NCCN Guidelines for Malignant Pleural Mesothelioma). Contraindications to bevacizumab include uncontrolled hypertension, risk for bleeding or clotting, and substantial cardiovascular morbidity.
Other acceptable first-line combination chemotherapy options recommended by NCCN include: 1) pemetrexed/carboplatin, which was assessed in 3 large phase 2 studies (median survival = 12.7, 14, and 14 months, respectively); or 2) gemcitabine/cisplatin, which was also assessed in phase 2 studies (median survival = 9.6–11.2 months).
Gemcitabine/cisplatin may be useful for patients who cannot take pemetrexed. A comparison of 1704 patients with medically inoperable MPM treated with cisplatin/pemetrexed or carboplatin/pemetrexed as part of an expanded access trial found that outcomes with the regimens were similar. For the 2018 update, the NCCN Panel deleted the caveat that carboplatin/pemetrexed regimen is a better choice for patients with poor PS and/or comorbidities, because panel members feel this regimen can also be used for patients with good PS based on clinical trial data. Acceptable first-line single-agent options include pemetrexed or vinorelbine for patients who are not candidates for platinum-based combination therapy. A phase 2 trial assessed adding bevacizumab to carboplatin/pemetrexed with or without maintenance bevacizumab as first-line therapy for patients with unresectable MPM. Overall survival was 15.3 months; 34% (26/76) of patients had a partial response and 58% (44/76) had stable disease.
Bowel perforation occurred in 4% of patients, grade 3 to 4 fatigue occurred in 8%; there were 3 toxic deaths. Maintenance bevacizumab (maximum, 1 year) was administered to patients without progression and/or severe toxicities. For the 2018 update, the NCCN Panel now recommends (category 2A) adding bevacizumab to carboplatin/pemetrexed with or without maintenance bevacizumab as a new first-line therapy option for patients with unresectable MPM based on this trial.