Clinical pattern of failure after a durable response to immune check inhibitors in non-small cell lung cancer patients

Abstract

Although immune checkpoint inhibitors (ICIs) can induce durable responses in non-small-cell lung cancer (NSCLC) patients, a significant proportion of responders still experience progressive disease after a period of response. Limited data are available on the clinical patterns of acquired resistance (AR) to ICIs. Clinical and radiologic data from 125 NSCLC patients treated with anti-PD-1 or PD-L1 antibodies between 2011 and 2018 at two tertiary academic institutions were retrospectively reviewed. Overall, 63 (50.4%) patients experienced AR after ICI treatment in a median of 10.7 months. Among the 13 patients with a partial response with ICI, 12 (32.4%) had only lymph node progression. Most patients (n = 52, 82.5%) had one or two sites with progression (oligo-progression). The median overall survival (OS) after progression was significantly longer in the extrathoracic group than in the thoracic and liver progression groups (30.2 months [95% confidence interval (CI), 13.4 to not reached (NR)], 11.7 months [95% CI, 9.5-21.1], and 5.4 months [95% CI, 2.6-NR], respectively, P < 0.001). Patients with oligo-progression had significantly longer OS after AR than did the multi-progression patients (18.9 months [95% CI, 10.6-NR] vs. 8.8 months [95% CI, 5.7-NR], P = 0.04). No significant difference in progression-free survival was observed between the subsequent chemotherapy and the ICI after AR groups (P = 0.723). Patients with AR after ICI treatment had a unique progression pattern with oligo-progression and high rates of progression only in the lymph nodes. Local treatment and/or continuation of ICIs beyond AR might be an effective option.

Figure 1

Donut plot showing sites of acquired resistance by best objective response to immune checkpoint inhibitors. LN lymph node, PR partial response, SD stable disease.

Figure 2

Kaplan–Meier survival curves showing overall survival from the point of acquired resistance for (A) the subgroup that had thoracic, extrathoracic, and liver progression only (B) the subgroup that had one or two progression sites or more than three progression sites (C) the subgroup that had progression from new lesions, existing lesions, and both new and existing lesions (D) the subgroup that had only lymph node and extranodal progression (including the lung).

Figure 3

Kaplan–Meier survival curves showing (A) overall survival from the point of acquired resistance based on the subgroups of subsequent treatment (B) progression free survival based on the subsequent treatment.