Clinical predictors of survival in patients with relapsed/refractory small-cell lung cancer treated with checkpoint inhibitors: a German multicentric real-world analysis

Abstract

Objectives: Small-cell lung cancer (SCLC) is a lung malignancy with high relapse rates and poor survival outcomes. Treatment-resistant disease relapse occurs frequently and effective salvage therapies are urgently needed. Materials and Methods: We aimed to define efficacy and safety of checkpoint inhibitors (CPIs) in a heterogeneous population of relapsed and refractory SCLC patients in a large retrospective multicentric real-world cohort across German tertiary care centers. Results: A total of 111 patients from 11 treatment centers were included. Median age of all patients was 64 years, and 63% were male. Approximately one-third of all patients had poor performance status [Eastern Cooperative Oncology Group (ECOG) ⩾ 2], and 37% had known brain metastases. Patients were heavily pretreated with a median number of prior therapy lines of 2 (range, 1–8). Median follow-up of the entire cohort was 21.7 months. Nivolumab and Nivolumab/Ipilimumab were the most common regimens. Overall disease control rate was 27.2% in all patients and was numerically higher in CPI combination regimens compared with single-agent CPI (31.8% versus 23.8%; p = 0.16). Median overall survival (OS) was 5.8 months [95% confidence interval (CI), 1.7–9.9 months]. The 12- and 24-month survival rates were 31.8% and 12.7%, respectively. The 12-week death rate was 27.9%. Disease control and response rate were significantly lower in patients with liver metastases. Platinum sensitivity (to first-line treatment), metastatic burden, and lactate dehydrogenase (LDH) showed prognostic impact on survival in univariate analysis. Neutrophil-to-lymphocyte ratio (NLR) was a significant and independent predictor of survival in univariate ( p = 0.01) and multivariate analyses [hazard ratio (HR), 2.1; 95% CI = 1.1–4.1; p = 0.03]. Conclusion: CPI in patients with relapsed or refractory (R/R) SCLC is of limited value in an overall patient cohort; however, long-term survival, in particular with CPI combination strategies, is possible. Clinical characteristics allow a more differentiated subgroup selection, in particular patients with low NLR showed less benefit from CPI in R/R SCLC.

A Real-World Analysis of Anti-Programmed Death-Ligand 1 (PD-L1) Immune Checkpoint Inhibitor Treatments Combined with Chemotherapy in Untreated Extensive Stage Small Cell Lung Cancer

“…Therefore, elevated serum LDH levels may re ect increased cancer cell activation and are associated with poor prognosis in cancer patients [28]. The results of our study are compatible with those of previous studies [17,21,22,[26][27][28][29], and LDH was identi ed as a factor associated with unfavorable outcomes in extensive-stage SCLC patients who received rst-line anti-PD-L1 ICIs combined with chemotherapy.…”

“…The NLR has been identi ed as a predictive factor associated with poor clinical outcome in patients with NSCLC and SCLC in several previous studies [21][22][23]. An increasing NLR has been proposed to be a response to systemic in ammation, and in previous studies, it has been shown to correlate with the severity of trauma, CVD and malignancies.…”

“…The serum LDH concentration is another prognostic factor frequently identi ed in patients with malignancies [17,21,22,26,27]. LDH is an essential enzyme in glycolysis and functions in catalyzing the conversion of pyruvate to lactate; elevated serum LDH levels have been used as an in ammatory index [28].…”

“…Previous studies have reported that additional radiation therapy induces abscopal effects and enhances the cytotoxicity of ICIs in the treatment of NSCLC [30,31]. Based on the concept of an abscopal effect, additional thoracic radiation therapy was administered to some extensive-stage SCLC patients receiving immunotherapy combined with chemotherapy in previous studies [17,21,22]. Superior vena cava (SVC) syndrome or a large thoracic tumor burden are paraneoplastic complications that frequently occur in extensive-stage SCLC patients, and thoracic radiation therapy must be administered to rescue the complications of great vessels or airway compression [32].…”

Long-term survival in extensive-stage small-cell lung cancer treated with different immune checkpoint inhibitors in multiple-line therapies: A case report and literature review

“…However, this patient achieved a high-quality long-term survival of almost 50 months after multiple lines of therapy, which is exceedingly rare. A review of the literature revealed that patients with ES-SCLC with better physical status ( 14 , 15 ), sensitivity to platinum-based drugs and the absence of liver or brain metastases ( 16 ), and adherence to active close follow-up may have a better prognosis with the possibility of achieving long-term survival. In these respects, the present patient is in accordance, and this may be one of the reasons for her long-term survival.…”