Long-Term Survival and Stable Disease in a Patient with Extensive-Stage Small-Cell Lung Cancer after Treatment with Carboplatin, Etoposide and Atezolizumab.

Survival beyond 2 years is rare in patients with extensive-stage small-cell lung cancer (ES-SCLC) treated with chemotherapy alone. We describe a patient with ES-SCLC who was treated with carboplatin, etoposide and the programmed death-ligand 1 inhibitor atezolizumab in the IMpower133 study (ClinicalTrials.gov registration: NCT02763579) and who achieved exceptionally long-term survival. Treatment-naïve patients with ES-SCLC (n = 403) were included in the IMpower133 study, and the identified patient had been randomised to the investigational treatment arm, where patients received induction therapy with carboplatin and etoposide plus atezolizumab for four 21-day cycles, followed by ongoing maintenance therapy with atezolizumab. The patient had achieved a partial response after induction therapy, and then received seven cycles of atezolizumab maintenance therapy until immune-related toxicities necessitated discontinuation. The patient was alive with an ongoing response and excellent performance status more than 6 years after starting treatment and 5 years after discontinuing atezolizumab maintenance. In conclusion, this patient with ES-SCLC from the IMpower133 study is a rare example of ongoing survival more than 6 years beyond diagnosis and the start of treatment with first-line atezolizumab. This demonstrates the potential durability of response with immunotherapy.

Real-World Analysis of Nivolumab and Atezolizumab Efficacy in Previously Treated Patients with Advanced Non-Small Cell Lung Cancer.

Nivolumab (anti-PD-1 antibody) and atezolizumab (anti-PD-L1 antibody) have shown superior survival outcomes and improved adverse effects compared to standard chemotherapy in advanced non-small cell lung cancer (NSCLC) patients. However, the efficacy of both treatments has not been directly compared in clinical trials. This retrospective, single-centre study was performed from June 2015 to December 2020 and included a cohort of 158 previously treated patients with stage IV or recurrent NSCLC who received PD-1 (nivolumab) (n = 89) or PD-L1 (atezolizumab) (n = 69) inhibitors at the Virgen del Rocío Hospital in Seville. The objective response rate (ORR) was 22.5% in the nivolumab group and 14.5% in the atezolizumab group (p = 0.140). Multivariate analysis did not show significant differences between the two groups for PFS and OS (PFS hazard ratio (HR): 0.80, 95% confidence interval (CI): 0.55−1.17, p = 0.260; OS HR: 0.79, 95% CI: 0.52−1.21, p = 0.281). Adverse events of all grades occurred in 68 patients in the nivolumab group (76.4%) and in 34 patients in the atezolizumab group (49.3%) (p < 0.001). Atezolizumab and nivolumab did not show statistically significant differences in survival outcomes in patients with NSCLC, even when stratified by histological subtype (squamous versus nonsquamous). However, the safety analysis suggested a more favourable toxicity profile for atezolizumab.

Correlation of peripheral blood biomarkers with clinical outcomes in NSCLC patients with high PD-L1 expression treated with pembrolizumab.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are currently the standard therapy in advanced non-small cell lung cancer (NSCLC); however, there is no well-established prognostic biomarker. We investigated the relationship between survival outcomes and three peripheral blood biomarkers, including the neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and monocyte-to-lymphocyte ratio (MLR), as well as a new score termed the risk blood biomarker (RBB), calculated from the combination of the neutrophil-monocyte-to-lymphocyte ratio (NMLR) and white blood cell count (WBC). METHODS: This study included patients with stage IV or recurrent NSCLC confirmed with programmed death ligand 1 (PD-L1) expression ≥50% who received pembrolizumab monotherapy as first-line treatment at the Virgen del Rocío University Hospital in Seville, Spain. To establish the relationship between baseline peripheral blood biomarkers and survival outcomes, progression free survival (PFS) and overall survival (OS), we used the Kaplan-Meier method and multivariable Cox regression models. RESULTS: A total of 51 patients were included in this study. In multivariate analysis, baseline NLR and PLR showed a strong association with PFS [NLR hazard ratio (HR): 0.19, 95% confidence interval (CI): 0.09-0.44, P<0.001; PLR HR: 0.46, 95% CI: 0.23-0.92, P=0.03] and OS (NLR HR: 0.07, 95% CI: 0.02-0.19, P<0.001; PLR HR: 0.29, 95% CI: 0.13-0.67, P=0.004), and the MLR was associated with OS (MLR HR: 0.34, 95% CI: 0.15-0.76, P=0.01). According to the RBB score, groups with lower scores were associated with superior PFS (group 0: HR: 0.16, 95% CI: 0.06-0.41, P<0.001 and group 1: HR: 0.29, 95% CI: 0.12-0.73, P=0.01) and OS (group 0: HR: 0.04, 95% CI: 0.01-0.17, P<0.001 and group 1: HR: 0.15, 95% CI: 0.05-0.42, P<0.001). CONCLUSIONS: Low baseline NLR, MLR and PLR are significantly associated with better PFS, and low baseline NLR and PLR are associated with better OS. Additionally, we identified three subgroups of patients using the RBB score, and low scores were associated with improved survival outcomes and response to therapy.

Phase II Trial of Palbociclib in Recurrent Retinoblastoma-Positive Anaplastic Oligodendroglioma: A Study from the Spanish Group for Research in Neuro-Oncology (GEINO).

BACKGROUND: The cell cycle checkpoint G1/S, dependent on cyclin-dependent kinase (CDK) 4 amplification/overexpression and retinoblastoma phosphorylation, is altered in most anaplastic oligodendrogliomas (AOs). OBJECTIVE: We aimed to evaluate the efficacy of palbociclib, an oral inhibitor of CDK4/6 with proven efficacy in breast cancer, in patients with AO. The primary endpoint was progression-free survival at 6 months. PATIENTS AND METHODS: We conducted a multicenter, open-label, phase II trial evaluating the efficacy and safety of palbociclib in patients with AO who progressed on radiotherapy and chemotherapy with histologically and molecularly confirmed grade 3 oligodendroglioma and conserved retinoblastoma protein (pRb) expression by immunohistochemistry. Patients were treated with palbociclib (125 mg/day) for 3/1 weeks on/off. RESULTS: Overall, 34 patients were enrolled across 10 hospitals in the Spanish Group of Neuro-Oncology (GEINO) study. The study was stopped early owing to the lack of efficacy, with 74% of evaluable patients progressing within 6 months, which was insufficient to consider palbociclib as an active drug in this population. Within the median follow-up of 12 months, the median progression-free survival was 2.8 months [95% confidence interval (CI) 2.6-3.1] and the median overall survival was 32.1 months (95% CI 5.1-59.2). There were no partial or complete responses; only 13 patients (38%) achieved stable disease as the best response. Palbociclib was well tolerated, with neutropenia (grade 3 or higher: 58.8%) and thrombocytopenia (grade 3 or higher: 14.7%) as the most common adverse events (AEs). Both AEs had no significant impact. CONCLUSION: Despite the good tolerance, palbociclib monotherapy did not show favorable efficacy against recurrent AO. TRIAL REGISTRATION: This study is registered with ClinicalTrials.gov, identifier NCT0253032 (retrospectively registered on 21 August 2015).