IMpower150: analysis of efficacy in patients (pts) with liver metastases (mets)

Background: Atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP]; ABCP) showed improved PFS and OS vs. bev + CP (BCP) in pts with chemo-naive NSCLC (IMpower150). Benefit with ABCP vs. BCP extended to key subgroups, including pts with baseline (BL) liver mets, which is a poor prognostic factor in metastatic NSCLC. Similar outcomes were not seen with atezo + chemo (IMpower150 [atezo + CP; ACP]; IMpower130; IMpower132), suggesting that the addition of bev to atezo + chemo is important for conferring clinical benefit in these pts. Here we further explore characteristics and responses of pts with BL liver mets in IMpower150.

Methods: 1202 ITT pts were randomized 1 : 1 : 1 to receive ABCP, ACP or BCP. Doses were: A, 1200 mg; B, 15 mg/kg; C, AUC 6 mg/mL/min; P, 200 mg/m². Coprimary endpoints were OS and investigator-assessed PFS in ITT-wild-type pts. Exploratory analyses included efficacy and safety in pts with liver mets.

Results: The data capture ≥ 20-mo follow-up in ITT pts (data cutoff: Jan 22, 2018). 162 pts had BL liver mets (ABCP, n = 52; ACP; n = 53; BCP, n = 57), with a median of 3 metastatic sites and median BL tumor SLD of 109 mm (range, 10 – 249). BL characteristics in these pts were generally balanced across study arms. PFS and OS were improved with ABCP vs. BCP ([Table 1]). Gr 3 – 4 treatment-related AEs occurred in 52.1%, 36.5% and 54.5% of pts with liver mets in the ABCP, ACP and BCP arms, respectively.

Table 1 

Presence of liver mets	mPfS, mo			HR (95% CI)
	ABCP	ACP	BCP	ABCP vs. BCP	ACP vs. BCP
a Pts with measurable disease at BL.
Yes	8.2 (n = 52)	5.4 (n = 53)	5.4 (n = 57)	0.41 (0.26, 0.62)	0.81 (0.55, 1.21)
No	8.4 (n = 348)	6.9 (n = 349)	7.0 (n = 343)	0.61 (0.52, 0.73)	0.90 (0.77, 1.06)
	mOS, mo			HR (95% CI)
Yes	13.3 (n = 52)	8.9 (n = 53)	9.4 (n = 57)	0.52 (0.33, 0.82)	0.87 (0.57, 1.32)
No	20.4 (n = 348)	21.0 (n = 349)	17.0 (n = 343)	0.82 (0.66, 1.02)	0.84 (0.68, 1.04)
	ORR, %a			Difference (95% CI), %
Yes	60.8 (n = 51)	26.9 (n = 52)	41.1 (n = 56)	19.7 (− 0.75, 40.18)	− 14.2 (− 33.65, 5.35)
no	55.8 (n = 346)	42.7 (n = 349)	40.1 (n = 337)	15.7 (8.03, 23.4)	2.6 (− 5.03, 10.29)
	mDOR, mo			HR (95% CI)
Yes	10.7 (n = 31)	5.6 (n = 15)	4.6 (n = 23)	0.39 (0.21, 0.73)	0.59 (0.29, 1.23)
No	11.5 (n = 193)	9.2 (n = 149)	6.5 (n = 138)	0.43 (0.33, 0.55)	0.52 (0.40, 0.69)

Conclusions: ABCP reduced the risk of death in pts with liver mets by 48% vs. BCP and may represent an important new treatment option for this population.

NCT02366143

• Reference

• 1 Socinski MA. et al. ASCO 2019.