Lazarus type response to immunotherapy in three patients with poor performance status and locally advanced NSCLC: a case series and literature review

Abstract

Background: Immune checkpoint inhibitors (ICIs) have become the standard treatment for patients with advanced non-small cell lung cancer (NSCLC). However, the safety and efficacy of ICIs in severe advanced NSCLC patients with poor performance status (PS) are still unclear.Methods: In the current study, we report a retrospective case series of three critically ill NSCLC patients with poor PS treated with immunotherapy in our hospital, and discussed these cases with reference to the existing literature and guidelines.Results: Before treatment, the Eastern Cooperative Oncology Group (ECOG) PS scores of all three patients were 4, while programmed cell death protein ligand-1 (PD-L1) was strongly expressed (over 50%).After initiating anti-programmed cell death 1 (PD-1)/PD-L1 agents, the PS score of the three patients improved rapidly to 0-1 in a short time. A Lazarus type response was observed in all patients. There were no grade 3-4 immune-related adverse events (irAEs) in any of the patients, and only one patient developed rash (grade 2 irAE) and hypothyroidism (grade 2 irAE). The best response across all three patients was partial response (PR). As of the latest follow-up date on June 10, 2020, two patients are still alive, with the other having died on January 14, 2020, whose progression-free survival (PFS) and overall survival (OS) were 11 and 16 months, respectively. Conclusions: Immunotherapy is still an effective and low-toxicity option for severe advanced NSCLC patients with poor PS. Lazarus type response may occur, especially in patients whose PD-L1 is strongly expressed (≥50%). However, a greater amount of real-world data or randomized clinical trials are needed in this setting.

The Revolution of Immunotherapy in Gynecological Cancers: The Lazarus Effect in Endometrial Cancer

“…Firstly, we report cases of patients, some also terminally ill, with poor PS and critically high disease burden, with rapid improvement of patients' health conditions during the very first days of treatment. Moreover, to the best of our knowledge, the only case series of the Lazarus effect during ICIs available in the literature [12,13] reported a median time to clinical response of 6 and 5 weeks, respectively. No patients interrupted treatment due to immunotherapy-related adverse events, leading to a good quality of life.…”

“…A Lazarus response was also described in three patients affected by advanced non-small cell lung cancer with strong expression of PD-L1 (>50%) with a PS ECOG 4 at the treatment baseline. They were treated with immune checkpoint inhibitors and demonstrated a very rapid improvement of PS ECOG to 1 or 0 [13]; in these cases, the median time to clinical response was 5 weeks (range 1-7 weeks).…”

International consensus on severe lung cancer—the first edition

“…The patient received combination therapy including endoscopic recanalization of central airway followed by immunotherapy, which reduced tumor lesions and improved the PS score (180). Case reports have shown that immunotherapy was also effective in patients with a PS of 4 (181,182). Nevertheless, the role of immunotherapy in patients with poor PS scores needs to be further investigated.…”

Reply to A.R. Khaki et al

“…Improvement in PS has been seen with ICI therapy. Nie et al 10 reported that three patients at their institution with NSCLC and ECOG PS of 4 with programmed cell death ligand 1 expression of more than 50% all experienced a Lazarus-type response. Gounant et al 11 has reported that in their study of 35 consecutive patients with PS 3-4 advanced NSCLC who received compassionate use nivolumab, nine patients (approximately 26%) had a PS improvement to 0-1, which corresponded to a median overall survival of 43 months.…”