Optimal drugs for second-line treatment of patients with small-cell lung cancer

Abstract

Second-line treatment is not an option for most SCLC patients. Given the evidence up to now, the potentials for immuno-oncology in SCLC are high. The hope is that these expectations are met, and that all drugs being developed will offer new and improved treatment options for SCLC patients.

Small cell lung cancer: model of circulating tumor cell tumorospheres in chemoresistance

“…Genetically, SCLC is characterized by inactivation of tumor suppressors p53 and retinoblastoma gene (Rb1) and additional mutations or increased expression of a wide range of different drivers for small subpopulations of patients 1, 4 . Current standard care for extended stage disease (ED-SCLC) or metastatic SCLC is platinum-based chemotherapy and thoracic/prophylactic cranial irradiation 5, 6 . Despite very high initial response rates, tumors recur rapidly within 1–2 years comprising local relapse or metastasis to liver, brain, bone and other secondary sites.…”

“…Despite very high initial response rates, tumors recur rapidly within 1–2 years comprising local relapse or metastasis to liver, brain, bone and other secondary sites. Second-line therapy employs the single approved chemotherapeutic topotecan or anthracycline-based therapy as alternative but yields poor responses of short duration 5, 6 . A host of studies performed over the last decades evaluating all kinds of conventional chemotherapeutics, novel drugs, targeted and antiangiogenic agents failed to provide a survival benefit in SCLC over standard chemotherapy 5–7 .…”

“…Second-line therapy employs the single approved chemotherapeutic topotecan or anthracycline-based therapy as alternative but yields poor responses of short duration 5, 6 . A host of studies performed over the last decades evaluating all kinds of conventional chemotherapeutics, novel drugs, targeted and antiangiogenic agents failed to provide a survival benefit in SCLC over standard chemotherapy 5–7 . The poor prognosis of SCLC, with a typical overall 5-year survival of 5–10% which has not changed considerably for the last decades, requires new modalities of treatment guided by a better understanding of the underlying biology of tumor spread and development of drug resistance.…”

Relapsed small-cell lung cancer: platinum re-challenge or not

“…There are no optimal drugs for the treatment of recurrent SCLC but only agents registered for this use such as topotecan, which remains the standard-of-care for the treatment of second-line platinum-sensitive SCLC patients worldwide, and amrubicin which is registered only in Japan (7).…”

“…Early trials of various immuno-oncology agents targeting immune checkpoint pathways have shown promising results in these patients. Phase III trials with immune checkpoint agents are underway in any lines of SCLC treatment (7).…”