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

Jan A Stratmann; Radha Timalsina; Akin Atmaca; Vivian Rosery; Nikolaj Frost; Jürgen Alt; Cornelius F Waller; Niels Reinmuth; Gernot Rohde; Felix C Saalfeld; Aaron Becker von Rose; Fabian Acker; Lukas Aspacher; Miriam Möller; Martin Sebastian

doi:10.1177/17588359221097191

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

Ther Adv Med Oncol. 2022 Jun 4:14:17588359221097191. doi: 10.1177/17588359221097191. eCollection 2022.

Authors

Affiliations

¹ Department of Internal Medicine, Hematology/Oncology, Goethe University, Theodor Stern Kai 7, 60596 Frankfurt am Main, Germany.
² Department of Internal Medicine, Hematology/Oncology, Goethe University, Frankfurt, Germany.
³ Department of Oncology and Hematology, Krankenhaus Nordwest, UCT-University Cancer Center, Frankfurt, Germany.
⁴ Department of Medical Oncology, West German Cancer Center, University Medicine Essen, Essen, Germany.
⁵ Charité - Universitätsmedizin Berlin, Berlin, GermanyHumboldt-Universität zu Berlin, Berlin, Germany.
⁶ Department of Internal Medicine III (Hematology, Oncology, Pneumology), University Medical Center Mainz, Mainz, Germany.
⁷ Internal Medicine I, Haematology, Oncology and Stem Cell Transplantation, Faculty of Medicine, Freiburg University Medical Center, Freiburg, Germany.
⁸ Department of Oncology, Asklepios Clinic München-Gauting, Gauting, Germany.
⁹ Department of Respiratory Medicine, Medical Clinic 1, University Hospital, Frankfurt, Germany.
¹⁰ Department for Internal Medicine I, University Hospital Carl Gustav Carus Dresden, TU Dresden, Dresden, Germany.
¹¹ Department of Internal Medicine III, Klinikum rechts der Isar, Technical University Munich, Munich, Germany.
¹² Department of Oncology, Martha-Maria Hospital Halle, Halle, Germany.

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.

Keywords: checkpoint inhibitor; immunotherapy; metastasis; prognostic biomarker; small-cell lung cancer.