Randomized phase 3 trial of amrubicin versus topotecan as second-line treatment for small cell lung cancer (SCLC)

Nivolumab alone and nivolumab plus ipilimumab in recurrent small-cell lung cancer (CheckMate 032): a multicentre, open-label, phase 1/2 trial

“…7,8,26 Consistent with other trials with immune checkpoint inhibitors across multiple solid tumours, and unlike topotecan trials, 8 this trial demonstrated a flattening of the overall survival curves for the nivolumab-3 and nivolumab-1/ipilimumab-3 cohorts, suggesting a survival benefit in a subset of patients. 9,10,12 However, due to the small numbers in this trial, it is difficult to determine when this occurs.…”

“…Response rates to topotecan depend on chemosensitivity, driven by tumour resistance mutations. 7,8 In contrast, the genomically unstable nature of SCLC 2 may make it sensitive to immune-checkpoint blockade via induction or restoration of a tumour antigen-driven immune response. As few lymphocytes are observed in SCLC tumours, 28 one hypothesis is that there is a greater need to target the lymphoid compartment with CTLA-4 inhibition in addition to PD-1 inhibition to maximise the treatment effect.…”

“…16 In all cohorts, fewer treatment-related toxicities were reported when compared with trials of topotecan or amrubicin. 7,8 Three patients had limbic encephalitis, and one patient receiving nivolumab plus ipilimumab died of myaesthenia gravis. Autoimmune encephalitis and myaesthenia gravis have been reported, albeit rarely, with both nivolumab and ipilimumab.…”

“…7 Though response rates with topotecan are 23% and 9% for platinum-sensitive and platinum-resistant/refractory patients, respectively, they are not durable. 8 Nivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint-inhibitor antibody, significantly improved overall survival and had a favourable safety profile compared with docetaxel in two phase 3 studies of patients with non-SCLC (NSCLC) who progressed after first-line platinum-based doublet chemotherapy, 9,10 leading to its approval in the US for treatment of patients with metastatic NSCLC and in the EU for treatment of patients with locally advanced or metastatic squamous NSCLC. 11 Ipilimumab, a fully human IgG1 cytotoxic T-lymphocyte antigen 4 (CTLA-4) immune-checkpoint inhibitor, significantly improved overall survival in two phase 3 studies in patients with advanced melanoma, leading to approval in the US and the EU for this indication.…”

Small cell lung cancer. Has anything changed? Future perspectives

“…Otra opción eficaz y muy utilizada es la combinación vincristinaadriamicina-ciclofosfamida (VAC). Otro fármaco eficaz en este contexto es la amrubicina, que está aprobada en Japón (24).…”