Efficacy of anti-PD-1/PD-L1 antibodies after discontinuation due to adverse events in non-small cell lung cancer patients (HANSHIN 0316)

Abstract

Background: Immune checkpoint inhibitors (ICIs) have emerged as promising therapeutic agents in non-small cell lung cancer (NSCLC). However, the duration for which ICIs should be continued remains a clinical problem.

Methods: We examined the efficacy of anti-PD-1/PD-L1 inhibitors after the discontinuation of antibodies due to adverse events (AEs) in patients with NSCLC. This was a multicenter retrospective study that analyzed NSCLC patients who were treated with PD-1/PD-L1 inhibitors by August 2016.

Results: The patients with NSCLC were 18 males and 1 female at a median 67 years of age (range: 49-80 years). Eighteen of 19 patients were treated with nivolumab, one was with atezolizumab. Approximately half of AEs were interstitial pneumonia. Fourteen patients (73.7%) were treated with steroid therapy. The median number of treatment cycles was 7 (range, 1-70), and the median duration of treatment was 2.8 months (range, 1 day-32.9 months). The overall response rate with confirmation during treatment was 21.1%. The median progression-free survival (PFS) was 10.2 months (95% confidence interval [CI] = 3.2-17.1 months) and 5.6 months (95% CI = 0-12.2 months) from the initiation and the discontinuation of PD-1/PD-L1 treatment, respectively. The median PFS after discontinuation according to the confirmed response during administration was not reached for partial response (PR) and 4.9 months (95% CI, 3.7-6.0) for stable disease (SD) patients (P = 0.02).

Conclusion: The PFS of the PR patients was completely different from that of the SD patients. The cases with PR prior to the onset of AE tended to show a durable response after the discontinuation of PD-1/PD-L1 inhibitors.

Keywords: Adverse event; Anti-PD-1/L1 inhibitor; Discontinuation; Non-small cell lung cancer.

Conflict of interest statement

Ethics approval and consent to participate

This research conformed to the provisions of the Declaration of Helsinki. This retrospective study was approved by the ethics committee of Kobe University (approval No.160122) and each institutions. Consent to participate: this is a retrospective study and consent to participate was waived by the Ethics Committee of Kobe University and each institution.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

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Figures

Fig. 1

Kaplan-Meier curves of progression-free survival (PFS). a PFS from the treatment. b PFS from the discontinuation

Fig. 2

Kaplan-Meier curves of overall survival (OS)

Fig. 3

Kaplan-Meier curves of PFS according to the confirmed response during treatment. a PFS from the treatment. b PFS from the discontinuation

Fig. 4

Spider plot. Tumor burden kinetics in patients with advanced non–small-cell lung cancer treated with PD-1/PD-L1 therapy. Baseline tumor measurements are standardized to zero. Tumor burden was measured as sum of longest diameters of target lesions compared with baseline. Percent change in target lesion tumor burden from baseline over time. Only includes patients with baseline target lesion and one or more post baseline target lesion assessments with no missing value (n = 16). Gray zone denote more than 30% decrease. Solid line and dotted line indicate on treatment and off treatment respectively. Star show occurrence of new lesion