Chemotherapy continues to be the mainstay of treatment for malignant pleural mesothelioma (MPM), as most patients have unresectable disease at diagnosis, according to a new clinical guideline from the American Society of Clinical Oncology (ASCO).
Patients who are surgical candidates should undergo procedures as part of multimodal therapy that includes chemotherapy with or without additional radiation therapy.
“Given the rarity of this disease [~3,000 cases a year], there have been few large randomized trials, especially for surgical management of this disease,” wrote members of the expert panel, chaired by Hedy L. Kindler, MD, of the University of Chicago, and Raffit Hassan, MD, of the National Cancer Institute.
“Although no new drugs have been approved for the treatment of MPM, since the approval of pemetrexed plus cisplatin in 2004, there have been significant recent advances in the understanding of the biology of mesothelioma and identifying new targets for therapy,” they added. “Ongoing clinical trials suggest promising activity of several new agents in MPM, but they are not sufficiently mature to make treatment recommendations.”
Published in the Journal of Clinical Oncology, the guideline is ASCO’s first ever for MPM and covers all aspects of disease management. The expert panel produced more than 60 recommendations covering five areas of clinical management: diagnosis, staging, chemotherapy, surgery, and radiation therapy. Key recommendations include:
Diagnosis — An initial thoracentisis for all symptomatic patients; thorascopic biopsy of all patients for whom antineoplastic treatment is planned; open pleural biopsy if thorascopic biopsy is not feasible; core needle biopsy if neither thorascopic or open pleural biopsy is feasible
Staging — Contrast CT scan of the chest and upper abdomen for initial staging; FDG-PET/CT advisable except for patients not being considered for definitive surgical resection; dedicated abdominal CT scan with or without pelvic imaging if initial staging suggests metastatic disease; MRI (preferably with contrast) may be obtained to assess tumor invasion into the diaphragm; chest wall, mediastinum, and other areas.
Chemotherapy — Chemotherapy should be offered, as it has been shown to improve survival and quality of life; a trial of observation may be offered for asymptomatic patients prior to initiation of chemotherapy; single-agent chemotherapy or palliative care may be offered to selected patients with poor performance status; preferred first-line chemotherapy of pemetrexed-cisplatin doublet, or referral to a clinical trial; addition of bevacizumab (Avastin) to pemetrexed-cisplatin improved survival in selected patients and may be offered; bevacizumab not recommend for patients with performance status 2, significant cardiovascular comorbidity, uncontrolled hypertension, age >75, or bleeding/clotting risk.
Surgery — Maximal surgical cytoreduction strongly recommended for selected patients with early-stage disease; single-modality surgery generally insufficient — additional treatment needed, either systemic or radiation therapy; neoadjuvant chemotherapy recommended for patients with transdiaphragmatic disease, multifocal chest-wall invasion, or histologically confirmed contralateral mediastinal or supraclavicular lymph node involvement; no benefit of surgery for patients with sarcomatoid mesothelioma.
Radiotherapy — Prophylactic irradiation of intervention tracts not recommended; adjuvant radiation therapy recommended after resection of histologically positive intervention tracts; palliative radiation therapy recommended for symptomatic disease; radiation therapy may be offered for localized asymptomatic recurrence; hemothoracic adjuvant or neoadjuvant radiation therapy may be offered to patients undergoing non-lung sparing cytoreductive surgery.
Kindler disclosed relationships with Aduro Biotech, MedImmune, Bayer HealthCare, Celgene, GlaxoSmithKline, AstraZeneca, Merck, Bristol-MyersSquibb, Boehringer Ingelheim, Ipsen, Erytech Pharma, Five Prime Therapeutics, Merck, Verastem, and Eli Lilly. Several coauthors disclosed relationships with multiple commercial entities.