The effect and safety of immune checkpoint inhibitor rechallenge in non-small cell lung cancer

Abstract

Introduction Immune checkpoint inhibitors (ICIs) have demonstrated long survival for the treatment of advanced non-small cell lung cancer (NSCLC). However, the effect and safety of ICI rechallenge have not been fully evaluated. The aim of this study was to investigate the efficacy and safety of ICI rechallenge in NSCLC patients. Methods We defined ‘rechallenge’ as re-administration of ICIs for patients who were previously treated with ICIs and discontinued treatment for any reason, and received subsequent chemotherapy. We retrospectively analyzed the histories of 434 patients with advanced NSCLC who received ICIs from December 2015 to December 2017 at seven centers. Results A total of 317 patients discontinued the ICI treatment, and 14 patients (4.4%) received ICI rechallenge. All 14 patients discontinued the first ICI due to disease progression. Eight patients received the same kind of ICIs, and six patients received different ICIs. Median progression-free survival and overall survival were 1.5 months [95% confidence interval (CI): 0.8–2.6] and 6.5 months [95% CI: 1.4–19.0], respectively. The objective response rate was 7.1%, and the disease control rate was 21.4%. Two of three patients who achieved at least a stable disease, received radiotherapy between the first and second ICIs. Adverse events were not significantly different compared with the first ICIs. Conclusions In this study, the effect of ICI rechallenge was limited. Careful consideration of the administration of ICI rechallenge is necessary. This report involved a small number of cases, so further large prospective studies are warranted to confirm the efficacy of ICI rechallenge and to investigate predictive markers to identify a patient population in which ICI rechallenge is effective.

Treatment discontinuation and re-initiation of anti-PD-(L)1 agents in metastatic cancers

“…There was a clinical benefit rate of 38% in patients with anti-PD-(L)1 re-challenge, suggesting that patients can respond to anti-PD-(L)1 re-treatment. Our results mirror other RWD results of anti-PD-(L)1 re-challenge where disease control rate has varied from ~ 20% to a bit over 40% with NSCLC patients (Fujita et al 2020;Niki et al 2018;Watanabe et al 2019). A recent retrospective study on melanoma patients treated mainly outside clinical trials, whose anti-PD-1 treatment had been discontinued for any reason, reported a response rate of only 14.7% of single-anti-PD-1, and ~ 25% to combination-ICI therapy re-challenge, while there was no causality between the initial best overall response to re-treatment response (Betof Warner et al 2020).…”

“…Due to the unique mechanism of anti-PD-(L)1 therapies, some patients experience long-lasting and durable responses, while a growing data shows that ICI re-challenge can bring meaningful clinical benefit to patients whose anti-PD-(L)1 therapy has been discontinued (Blasig et al 2017;Fujita et al 2020;Iivanainen and Koivunen 2019;Niki et al 2018;Watanabe et al 2019). Determination of the optimal Antti Tikkanen and Sanna Iivanainen have contributed equally to the study.…”

Retrospective Efficacy Analysis of Immune Checkpoint Inhibitor Rechallenge in Patients with Non-Small Cell Lung Cancer

“…In addition, ORR, DCR, and PFS of atezolizumab rechallenge after refractory anti-PD-1 antibodies for 18 patients with NSCLC were 0%, 38.9%, and 2.9 months, respectively [17]. Another report showed that ORR, DCR, and PFS values of ICI rechallenge in 14 patients with ICI refractory tumors were 7.1%, 21.4%, and 1.6 months, respectively [7]. Our current observations showed that ORR, DCR, PFS, and OS values of ICI rechallenge in 35 patients with NSCLC were 2.9%, 42.9%, 2.7 months, and 7.5 months, respectively.…”

“…Therefore, it is warranted to identify predictive clinical markers for the effectiveness of ICI rechallenge. Previous retrospective studies regarding ICI rechallenge have analyzed only limited numbers of NSCLC patients [7,8]. Hence, little is currently known regarding the effectiveness and tolerability of ICI rechallenge after disease progression following initial ICI treatments.…”

Drastic Response of Rechallenge of Nivolumab in a Patient with NSCLC Who Progressed on the First Nivolumab Treatment

“…1 The effect of immune checkpoint inhibitor (ICI) rechallenge after progression during the first ICI treatment is also thought to be limited. 2 However, there is no large prospective study to confirm the efficacy of ICI rechallenge, nor is there a predictive marker to identify a patient in whom ICI rechallenge is effective. 3 We have encountered a patient with NSCLC who showed a drastic response to rechallenge with nivolumab after acquisition of resistance to the first nivolumab treatment.…”