Role of molecular biology in the management of pancreatic cancer

Table 1 Main actionable molecular alterations in pancreatic ductal adenocarcinoma and their current European Society for Medical Oncology scale for clinical actionability of molecular target classification

Biomarker	Targeted therapy	ESCAT classification	Ref.
BRCA1, BRCA2 germinal	Olaparib	IA	[87]
BRCA1, BRCA2 germinal/somatic	Rucaparib	IB	[86,88]
PALB2 germinal/somatic	Rucaparib	IB	[88]
NTRK fusions	Larotrectinib, entrectinib	IC	[27,89]
MSI high	Pembrolizumab	IC	[25]
RET fusions	Pralseltinib, selpercatinib	IC	[90,91]
NRG1 fusions	Zenocutuzumab	IIB	[30]
KRASG12C	Sotorasib, adagrasib	IIB	[55,56]
FGFR2 Fusions	Pemigatinib, infigratinib, futibatinib	IIIA	[92,93]
PIK3CA mutations	Alpelisib, buparlisib	IIIA	[94,95]
BRAFV600Emutation	Dabrafenib + trametinib, Binimetinib + encorafenib	IIIA	[96,97]
ALK/ROS1 fusions	Crizotinib, ceritinib, alectinib	IIIA	[98-100]
ERBB2 amplification	Trastuzumab + pertuzumab, T-DM1	IIIA	[101,102]

ESCAT: European Society for Medical Oncology Scale for Clinical Actionability of molecular Targets; MSI: Microsatellite instability.

Table 2 Safety and toxicity data regarding KRASG12C inhibitors in pancreatic ductal adenocarcinoma

	Adagrasib (n = 21)[57]	Sotorasib (n = 38)[63]
Objective response rate (95%CI)	33 (15-57)	21 (10-37)
Disease control rate	81	84
Median duration of response (months)	NA	5.7 (1.6-non evaluable)
Progression-free survival (months) (95%CI)	5.4 (3.9-8.2)	4.0 (2.8-5.6)
Overall survival (months) (95%CI)	8.0 (5.2-11.8)	6.9 (5.0-9.1)
Grade 3-4 toxicities	27	16
Dose reduction	40 (solid tumours)	13
Discontinuation for toxicity	0	0