Table 2.

Efficacy of escalation vs. non-escalation and escalation strategies for OS and PFS (adjusted for trial effect)

Parameter	Therapeutic escalation vs. non-escalation		Therapeutic escalation strategy
	All escalation strategies		Chemotherapy		Anti angiogenic
	RAS WT	RAS MUT	RAS WT	RAS MUT	RAS WT	RAS MUT
OS
HR (95% CI) [p-value]	0.74 (0.68–0.82) [< 0.0001]	0.89 (0.81–0.97) [0.007]	0.74 (0.64–0.87) [0.0001]	0.89 (0.78–1.02) [0.098]	0.78 (0.70–0.87) [< 0.0001]	0.91 (0.82–1.01) [0.07]
log(HR)	− 0.298	− 0.12	− 0.29	− 0.11	− 0.25	− 0.095
log(HRMUT)—log(HRWT)	0.178		0.183		0.157
p value for interaction	0.003		0.07		0.039
p value for heterogenity	0.93		0.25		0.66
PFS
HR (95% CI) [p-value]	0.55 (0.50–0.61) [< 0.0001]	0.61 (0.56–0.68) [< 0.0001]	0.53 (0.42–0.67) [< 0.0001]	0.62 (0.49–0.77) [< 0.001]	0.59 (0.47–0.73) [< 0.0001]	0.64 (0.51–0.80) [< 0.0001]
log(HR)	− 0.597	− 0.487	− 0.63	− 0.48	− 0.54	− 0.443
log(HRMUT)—log(HRWT)	0.111		0.142		0.093
p value for interaction	0.093		0.39		0.56
p value for residual heterogenity	0.029		< 0.0001		< 0.0001

RAS rat sarcoma, WT wildtype, MUT mutated, OS overall survival, PFS progression free survival, log HR natural logarithm of hazard ratio, VEGF vascular endothelial growth factor