Tsunami of immunotherapy reaches mesothelioma

Table 1 Main pre-phase III clinical trials of immunotherapy-based strategies for the treatment of mesothelioma

Clinical trial (Phase): Drug analyzed	Setting	Primary endpoint
MESOT-TREM 2008 (Phase II): Tremelimumab 15 mg/kg every 90 d[23]	Salvage setting	ORR: 6.9%
MESOT-TREM 2012 (Phase II): Tremelimumab 10 mg/kg every 4 wk[24]	Salvage setting	ORR: 13.7%
DETERMINE (Phase IIb): Tremelimumab 10 mg/kg every 4 wk vs Placebo[25]	Salvage setting	OS: 7.7 mo vs 7.3 mo (HR = 0.92; P = 0.41)
DREAM (Phase II): Durvalumab 1125 mg + Cisplatin 75 mg/m2 or Carboplatin AUC 5 + Pemexetrad 500 mg/m2 every 3 wk[26]	Front-line setting	6-mo PFS: 57%
JAVELIN Solid (Phase Ib): Avelumab 10 mg/kg every 2 wk[27]	Salvage setting	ORR: 9%

AEs: Adverse events; AUC 5: Area under the curve value of 5; HR: Hazard ratio; ORR: Overall response rate; OS: Overall survival; PFS: Progression free survival.

Table 2 Recently published practice changing phase 3 studies in Malignant Pleural Mesothelioma

Clinical trial (Phase)	Population	Treatment arms	mOS		mPFS		AEs G3
CheckMate 743 (Phase III)[35]	Untreated MPM	Nivolumab 3 mg/kg every 2 wk + ipilimumab 1 mg/kg every 6 wk	18.1 mo	HR: 0.74, P = 0.002	6.8 mo	HR: 1.00	30%
		Cisplatin + pemetrexed	14.1 mo		7.6 mo		32%
CONFIRM (Phase III)[29]	Relapsed MPM	Nivolumab 3 mg/kg every 2 wk	9.2 mo	HR: 0.72, P = 0.002	3 mo	HR: 0.61; P < 0.001	19%
		Placebo	6.6 mo		1.8 mo		6.3%

MPM: Malignant pleural mesothelioma; MM: Malignant mesothelioma (pleural or peritoneal); AEs: Adverse events; mOS: Median overall survival; mPFS: Median progression free survival; G: Grade; HR: Hazard ratio.

Table 3 Comparison of safety and efficacy of frontline Nivolumab + Ipilimumab vs chemotherapy in malignant pleural mesothelioma

Clinical trial	Phase	Treatment arm	mOS		mPFS		ORR	AEs G3
CheckMate-743[35]	III (open-label)	Nivolumab 3 mg/kg every 2 wk + Ipilimumab 1 mg/kg every 6 wk	18.1 mo	HR: 0.74, P = 0.002	6.8 mo	HR: 1.00	32%	30%
		Cisplatin + Pemetrexed	14.1 mo		7.6 mo		8%	32%
EMPHACIS[5]	III (single blind)	Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2	12.1 mo	HR: 0.77, P = 0.002	5.7 mo	HR: 0.68, P = 0.001	41.3% vs 16.7% (P < 0.001)
		Cisplatin 75 mg/m2	9.3 mo		3.9 mo		16.7%
MAPS[12]	III (open-label)	Pemetrexed 500 mg/m2 and Cisplatin 75 mg/m2 with 15 mg/kg Bevacizumab in	18.8 mo	HR: 0.77, P = 0.0167	9.2 mo	HR: 0.61, P < 0.0001	NR	71%
		Pemetrexed 500 mg/m2 + Cisplatin 75 mg/m2	16.1 mo		7.3 mo			62%

AEs: Adverse events; mOS: Median overall survival; mPFS: Median progression free survival; ORR: Overall response rate; G: Grade; HR: Hazard ratio.