Malignant mesothelioma treatment summary

 Malignant mesothelioma- epithelioid, sarcomatoid, mixed( biphasic)

BAP1 IHC loss is a molecular marker that is useful for diagnosing mesothelioma.

Histology: Aberrant BAP1 protein expression, which is defined as absence of nuclear BAP1 IHC staining, occurs in about 50% to 70% of patients with epithelioid mesothelioma but in less than 20% of those with sarcomatoid mesothelioma.

• Cisplatin with pemetrexed 12.1 months OS ( vrsus 9 for Cis alone). No maintenance. Carbo if cis ineligible.
• Cisplatin pem bev--> bev maintenance  18 months median OS ( MAPS  trial). Not FDA approved but listed on NCCN.
• Checkmate 743- practice changing esp for sarcomatoid. 18 months OS when compared with pem cis. In the control arm, bev was not included. So the benefit in epithelioid patients not clear.

So for epithelioid histology and patients over 75 use platinum doublet with bev front line, although NCCN 2022 update lists nivo 3mg/kg q 2 weeks + ipi 1 mg/kg q 6 weeks also as an option for 2 yr.

• In the second line setting after chemo, doublet IO recommended. Single agent IO nivo better than best supportive care but not necessarily any better than 2nd line chemo.
• No OS benefit with IO+ chemo front line. 

• No data to support any particular chemo after 1st line doublet IO, but vinorelbine median OS 11.6 months
• no role for maintenance pemetrexed after 1st line platinum doublet but bev maintenance ok for epithelioid. Another option is gemcitabine maintenance after 4-6 cycles platinum doublet.
• Gem+ ramucriumab is a 2nd line option
• If sarcomatoid but cannot get IO, add pegargiminase to platinum doublet

March 2025 ASCO updated guideline

• If candidate for rx, get either a thoracoscopic pleural biopsy or open pleural biopsy if the initial fluid cytology suggests mesothelioma
• Get PET if candidate for surgery. Otherwise CT A/P.
• Contralateral thoracoscopy and laparoscopy if suspected contralateral or abd disease respectively
• If candidate for maximal surgical cytoreduction, evaluate the mediastinum with mediastinoscopy or endobronchial ultrasound
• Surgery should be offered to pt with T1-T3N0 epithelioid disease
• Sarcomatoid should not be offered surgery.
• All patients with mesothelioma should be offered germline testing
• Tumor treatment fields not recommended