Investigation of poor predictive factors in extensive stage small cell lung cancer under etoposide‐platinum‐atezolizumab treatment

Abstract

Background: The phase III trial IMpower133 showed that platinum and etoposide plus atezolizumab was associated with improved overall survival (OS) and progression free-survival (PFS) when compared to the placebo group in treatment-naïve extensive stage (ES) small cell lung cancer (SCLC). Due to superiority in clinical outcomes, combination immunotherapy plus chemotherapy have become mainstay treatment modalities as first-line treatment in ES-SCLC. Nevertheless, real-world data are still lacking and the search for potential biomarkers is essential. This study aimed to evaluate potential predictive biomarkers applicable in ES-SCLC under combination therapy. Methods: Patients with ES-SCLC under etoposide-platinum-atezolizumab enrolled from seven university hospitals affiliated to the Catholic University of Korea were evaluated. Pretreatment clinical parameters were evaluated for association with OS and PFS. Adverse events (AEs) during induction and maintenance phases were also evaluated. p-values below 0.05 were considered statistically significant. Results: A total of 41 patients were evaluated. Six-month survival was 68.6%. As best response to treatment, 26 (63.4%) showed partial response, nine (22.0%) showed stable disease, and four (9.8%) showed progressive disease. During the induction phase, grade I-II AEs occurred in 22 (53.7%) patients, and grade III-IV AEs occurred in 26 (63.4%) patients. During the maintenance phase, nine out of 25 (36.0%) patients experienced any grade AEs. In multivariate analysis for OS, lactate dehydrogenase

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 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].…”

Efficacy and safety of anti-PD-1 inhibitor versus anti-PD-L1 inhibitor in first-line treatment of extensive-stage small cell lung cancer: a multicenter retrospective study

“…In stratified analysis, we found that ES-SCLC patients with normal LDH value benefit more from ICI than patients with abnormally high LDH levels; this is consistent with Lim et al [ 30 ].. A previous study suggested that LDH might be an indicator of tumor burden and that increased LDH inhibits antitumor activity of immune checkpoints by altering metabolism, nutrient availability, and acidic microenvironment [ 31 ]. In CheckMate-331, among SCLC patients with below-normal LDH, OS tended to be longer in patients receiving nivolumab as second-line treatment than in patients receiving chemotherapy [ 26 ].…”

Clinical impact of first‐line PD‐1 or PD‐L1 inhibitors combined with chemotherapy in extensive‐stage small cell lung cancer patients: A real‐world multicenter propensity score‐matched study

“… 18 , 19 Although ES‐SCLC has traditionally had a poor prognosis, recent phase three trials have confirmed improved outcomes with the addition of ICIs to chemotherapy. 8 , 9 , 11 , 20 However, only a few retrospective studies reported the survival outcomes in the real world, some without control groups, 21 , 22 some with insufficient case numbers, 23 , 24 and some including only PD‐L1 inhibitors. 25 , 26 , 27 Concerns about the inconsistency of anti‐PD‐1 agents and anti‐PD‐L1 agents suggested by the consequences of clinical trials are inconclusive.…”