Addition of Atezolizumab Improves PFS in NSCLC With Liver Mets

Mark A. Socinski, MD

According to a subgroup analysis from the phase III IMpower150 trial presented at the 2019 ASCO Annual Meeting, the addition of immunotherapy to bevacizumab (Avastin) and a chemotherapy doublet improved progression-free survival (PFS) in patients with non—small cell lung cancer (NSCLC) and baseline liver metastases.¹

“ABCP is an important new treatment option for patients with advanced nonsquamous NSCLC, particularly those with liver metastases,” the investigators, led by Mark A. Socinski, MD, executive medical director of the AdventHealth Cancer Institute in Orlando, FL, wrote in their presentation.

The 4-drug combination that included atezolizumab (A; Tecentriq) plus bevacizumab, carboplatin, and paclitaxel (BCP) resulted in a median PFS of 8.2 months as compared with 5.4 months for patients treated with BCP alone. Median OS was 13.3 months with ABCP and 9.4 with BCP.

According to the data, patients with liver metastases had a greater survival benefit with ABCP than did patients without liver metastases.

“ABCP was well tolerated, regardless of baseline liver-metastases status,” the investigators said. “The safety profile of ABCP in patients with liver metastases remained consistent with that observed in the ITT [intention-to-treat] population; there were no new safety signals in this patient subgroup.”

The results are consistent with those observed in other recent trials of immunotherapy in patients with NSCLC and liver metastases, said ASCO-invited discussant Kathryn C. Arbour, MD, of Memorial Sloan Kettering Cancer Center in New York. In general, trials have shown that patients with and without liver metastases benefited from PD-1/PD-L1—targeted therapy.

“The presence of liver metastases is associated with a poor prognosis in patients with NSCLC,” said Arbour. “Stratification in clinical trials based on presence of liver metastases is reasonable. There is no clear evidence thus far in randomized trials that patients with liver metastases should be treated differently than patients without liver metastases.”

Socinski and colleagues previously reported findings of the IMpower150 trial, which compared ABCP, BCP, and atezolizumab plus carboplatin and paclitaxel (ACP) in 1202 patients with stage IV nonsquamous NSCLC and no prior exposure to chemotherapy, last year in the New England Journal of Medicine. Liver metastases were a prespecified stratification factor.²

The primary data analysis showed that the ABCP regimen reduced the HR for PFS by 38% and the HR for OS by 22% versus BCP in the entire cohort (P<.001, P = .02). A preliminary subgroup analysis showed that patients with liver metastases benefited from ABCP.

The data from the subgroup analysis showed that treatment with ABCP in patients with baseline liver metastases was associated with a 59% reduction in the risk for progression or death as compared with BCP (HR, 0.41; 95% CI, 0.26-0.62). Patients without liver metastases had a median PFS of 8.4 months with ABCP versus 7 months with BCP, which resulted in a 39% reduction in the risk for progression or death (HR, 0.61; 95% CI 0.52-0.73).¹

The 3.9-month difference in OS among patients with liver metastases represented a 48% reduction in the risk of disease progression or death in favor of ABCP (HR, 0.52; 95% CI, 0.33-0.82). The magnitude of the benefit was similar after adjusting for baseline tobacco use and ECOG performance status. ABCP conferred a numerical OS advantage versus BCP in the patients without liver metastases (20.4 vs 17.0 months; HR 0.82, 95% CI 0.66-1.02).

Response rate and duration of response were similar in patients with or without liver metastases. ABCP produced the highest response rates, 60.8% in patients with liver metastases and 55.8% in patients without liver metastases. BCP had led to response rates of 41.1% and 40.1% in patients with and without liver metastases, respectively, and corresponding response rates in the ACP—arm were 26.9% and 42.7%.

Median duration of response in patients with liver metastases ranged from 10.7 months with ABCP to 5.6 months with ACP and 4.6 months with BCP. Patients without liver metastases had median response durations of 11.5 months, 9.2 months, and 6.5 months, respectively.

Grade 3/4 treatment-related adverse events (TRAEs) occurred in 52.1% of patients in the liver metastasis subgroup treated with ABCP, 36.5% of those treated with ACP, and 54.5% of those receiving BCP. Corresponding rates for patients without liver metastases were 57.4%, 44%, and 47.5%, respectively. Treatment discontinuation because of AEs occurred more often in the ABCP and BCP groups, regardless of liver metastasis status.

References:

1. Socinski MA, Jotte RM, Cappuzzo F, et al. IMpower150: analysis of efficacy in patients (pts) with liver metastases (mets).J Clin Oncol. 2019;37(suppl 15;abstr 9012). doi: 10.1200/JCO.2019.37.15_suppl.9012. /li>
2. Socinski MA, Jotte RM, Cappuzzo F, et al; the IMpower Study Group. Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC.N Engl J Med. 2018;35(24):2288-2301. doi: 10.1056/NEJMoa1716948.