Patients With NSCLC Who Complete 2 Years of ICI Treatment Experience Long-term PFS

Targeted Therapies in Oncology, March 2022, Volume 11, Issue 4

A significant proportion of patients who complete 2 years of immune checkpoint inhibitor treatment experience long-term progression-free survival.

Traditionally, oncologists will use immune checkpoint inhibitors (ICIs) until disease progression or toxicity occurs, but it is not known if prolonged use leads to longer survival times. Findings from a retrospective study that evaluated ICI use for 2 years in 96 patients with non–small cell lung cancer (NSCLC) demonstrated that at 12 months, progression-free survival (PFS) and overall survival (OS) rates were 81.1% and 96.4%, respectively, with an objective response rate (ORR) of 85.4%. According to the investigators, this suggests that a significantly high proportion of patients who completed 2 years of ICI treatment experienced long-term PFS.

Within this subgroup, 6.3% of patients had a complete response (CR), 79.2% of patients had a partial response (PR), and 14.6% of patients had stable disease (SD). After discontinuation, the PFS and OS rates at 12 months were 83.7% and 97.4%, respectively. For patients with SD, the CR and PR rates were 63.0% and 90.0%, respectively.

Patients Who Discontinued ICIs Without Disease Progression


Median OS was not reached, and the estimated OS at 12 months from discontinuation of ICI therapy was 96.4%, reported Kim et al.1 In 43 patients who discontinued ICI therapy without disease progression, 90.7% of patients experienced a response. In this subgroup, the median treatment response was 10.5 months, and the median follow-up duration was 21.2 months. Investigators reported a CR in 2 patients (4.7%), a PR in 37 patients 86.0%), and SD in 4 patients (9.3%) (TABLE).1

A total of 139 patients with advanced NSCLC were evaluated in South Korea. In the 96 patients who received ICI therapy for 2 years, the median age was 65 years (range 38-87), 90% had an ECOG performance status of 0 or 1, 65 patients (67.7%) had NSCLC, 27 patients (28.1%) had brain metastasis, and 97.9% of patients had high PD-L1 expression (defined as ≥50%).

Lines of therapy were administered as follows: 10 patients received ICIs in the front-line setting, 61 patients received ICIs in the second-line setting, and 25 patients received ICIs as a later line of therapy. Sixty-one patients received pembrolizumab (Keytruda), 29 received nivolumab (Opdivo), 4 received atezolizumab (Tecentriq), 1 received quavonlimab (MK-1308), and 1 was treated with pembrolizumab and quavonlimab.

Among patients who were treated for more than 6 months (n = 43) and stopped ICI treatment without disease progression, the median PFS and OS were not reached, wrote the investigators. At 12 months after ICI discontinuation, the PFS and OS rates were 71.0% and 90.7%, respectively, suggesting that once patients achieved a durable response at more than 6 months, a substantial amount of them experienced long-term PFS despite discontinuing ICIs.

According to a subgroup analysis, risk of disease progression after 2 years of treatment on ICIs was associated with ORR. Median PFS was significantly longer for CR and PR than SD (P =.044). These findings were similar in a cohort of patients who discontinued treatment without disease progression, in which median OS was significantly longer for CR and PR than SD (P =.019). In addition, patients who were treated for less than 12 months had significantly shorter PFS (26.3 months; 95% CI, 20.9-31.7) than those treated for more than 12 months (PFS, 38.1 months; 95% CI, 33.9-42.3; P = .011). The investigators suggest that patients who have received more than 1 year of treatment, are responsive to ICIs, and have only experienced mild adverse events (AEs) should continue therapy.

The investigators pointed out a number of limitations associated with the study. First, it is retrospective in nature and a small sample size, which can lead to bias. Second, only Asian patients with NSCLC were analyzed, which limits the study’s generalizability due to differences in molecular profiles and clinical features between Western and Eastern patients with NSCLC.

Nonetheless, the investigators concluded that a significant proportion of patients who complete 2 years of ICI treatment experience long-term PFS. Further, a durable response was observed in patients treated with ICIs for only 6 months who did not have disease progression. The findings, noted investigators, have implications for long-term survival.

REFERENCE

1. Kim H, Kim DW, Kim M, et al. Long-term outcomes in patients with advanced and/or metastatic non-small cell lung cancer who complet- ed 2 years of immune checkpoint inhibitors or achieved a durable response after discontinuation without disease progression: multi- center, real-world data (KCSG LU20-11). Cancer. 2022;128(4):778- 787. doi:10.1002/cncr.33984