Abstract
Despite approximately 40% of patients having Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of at least 2 in the real world, most landmark clinical trials that led to the use of pembrolizumab as standard of care in advanced non-small cell lung cancer (NSCLC) excluded this group. To evaluate whether an ECOG PS score of at least 2 at the start of therapy is associated with progression-free survival (PFS) and overall survival (OS) in advanced NSCLC treated with pembrolizumab monotherapy. This cohort study included all consecutive patients with advanced NSCLC who underwent treatment with palliative pembrolizumab monotherapy from February 2016 to October 2019 at a single academic cancer center, with data censoring on January 15, 2020. ECOG PS score at start of therapy, with 0 and 1 indicating fully active or restricted in strenuous activity and scores of 2 and higher indicating increasing disability. PFS and OS, measured from initiation of pembrolizumab monotherapy. Of 74 patients (median [range] age, 68.5 [33-87] years; 36 [48.7%] women; 53 [71.6%] White individuals) with median follow-up of 19.5 (95% CI, 13.4-27.8) months, 45 (60.8%) had an ECOG PS of 0 or 1, while 29 (39.2%) had an ECOG PS of at least 2. There were no significant differences in the baseline characteristics, except in age. Compared with patients with PS scores of 0 or 1, those with PS scores of at least 2 had significantly lower disease control rates (38 [88.4%] vs 15 [53.6%]; P = .002), shorter median PFS (7.9 [95% CI, 4.6-15.4] months vs 2.3 [95% CI, 1.8-4.8] months; P = .004), and shorter median OS (23.2 [14.0 vs 35.7] months vs 4.1 [95% CI, 2.1-6.9] months; P < .001). Among those potentially eligible for subsequent cancer-directed therapy beyond pembrolizumab monotherapy, patients in the group with PS scores of at least 2 were less likely to receive it than those with PS scores of 0 or 1 (2 [8.3%] vs 14 [45.2%]; P = .003). Multivariable adjustment for baseline characteristics confirmed ECOG PS of at least 2 as an independent risk factor for worse PFS (HR, 2.02; 95% CI, 1.09-3.74; P = .03) and worse OS (HR, 2.87; 95% CI, 1.40-5.89; P = .004). In this cohort study, having an ECOG PS score of at least 2 was associated with poorer prognosis for treatment of advanced NSCLC with palliative pembrolizumab monotherapy. Further prospective studies are needed to evaluate more objective and consistent measures of functional status to facilitate identification of patients with borderline performance status who may achieve durable clinical benefit from treatment with pembrolizumab monotherapy.
Highlights
Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 2 or higher compose 34% to 48% of all patients with advanced non–small cell lung cancer (NSCLC).[1,2] The ECOG PS scale indicates increasing levels of disability, with 0 indicating fully active; 1, restricted in strenuous activity; 2, restricted in work activity but ambulatory and capable of self-care; 3, capable of limited self-care; 4, completely disabled; and 5, dead
Most landmark clinical trials that led to the approval of pembrolizumab and other immune checkpoint inhibitors (ICIs) by the US Food and Drug Administration (FDA) were conducted in patients with ECOG PS scores of 0 or 1.1,3-5 Due to better perceived tolerance of ICIs compared with cytotoxic chemotherapy, results from these clinical trials have been extrapolated to those with PS scores of 2 or higher, leading to more liberal use of pembrolizumab in this subgroup of patients, who previously might not have been considered eligible for this treatment
Our study reported a 39.2% prevalence rate of ECOG PS scores of at least 2 in patients with advanced NSCLC at the start of pembrolizumab monotherapy, which is consistent with reports from other colleagues in the real-world setting.[1,2]
Summary
Patients with Eastern Cooperative Oncology Group (ECOG) performance status (PS) scores of 2 or higher compose 34% to 48% of all patients with advanced non–small cell lung cancer (NSCLC).[1,2] The ECOG PS scale indicates increasing levels of disability, with 0 indicating fully active; 1, restricted in strenuous activity; 2, restricted in work activity but ambulatory and capable of self-care; 3, capable of limited self-care; 4, completely disabled; and 5, dead. Most landmark clinical trials that led to the approval of pembrolizumab and other immune checkpoint inhibitors (ICIs) by the US Food and Drug Administration (FDA) were conducted in patients with ECOG PS scores of 0 or 1.1,3-5 Due to better perceived tolerance of ICIs compared with cytotoxic chemotherapy, results from these clinical trials have been extrapolated to those with PS scores of 2 or higher, leading to more liberal use of pembrolizumab in this subgroup of patients, who previously might not have been considered eligible for this treatment This is reflected in the findings from a nationwide patient-level database study that reported an overall increase in the use of systemic therapy at the end of life for patients with NSCLC, driven predominantly by ICIs (along with a concomitant decrease in use of chemotherapy) in the post–ICI approval period.[6] treatment with ICI within 30 days prior to death was associated with decreased referral to hospice and increased in-hospital deaths.[7] While oncologists routinely use PS for decisions regarding chemotherapy,[8] rigorous evidence regarding palliativeintent ICI use according to PS is still lacking
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