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

ABSTRACT

Introduction: Despite the high response rate to chemotherapy, there have been few advances in the treatment of small-cell lung cancer (SCLC) in the last decades. The state-of-the-art second-line therapy and future research developments in relapsed SCLC are reviewed.

Areas covered: There are no optimal drugs for second-line treatment of recurrent SCLC but only agents registered for this use. Topotecan remains the standard-of-care for the treatment of second-line platinum-sensitive SCLC patients worldwide, while amrubicin is another option, but registered only in Japan. To date, no targeted agents reporting interesting results in second-line SCLC treatment are available. The next-generation DNA sequencing should discover somatic gene alterations and their roles in SCLC to help in selecting patients who could benefit from a targeted agent. Two immunotherapeutics, ipilimumab and nivolumab, have shown promising preliminary results and are being investigated in ongoing trials.

Expert opinion: 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.

KEYWORDS:

• Amrubicin
• chemotherapy
• immunotherapy
• ipilimumab
• nivolumab
• SCLC
• targeted therapy
• topotecan

Article highlights

• Despite SCLC is marked sensitive to chemotherapy, it is characterized by high relapse rates and a subsequent poor prognosis because of drug resistance.

• The response and its duration to first-line chemotherapy, with a cut-off of 60 or 90 days after the completion of chemotherapy, identify two main groups: ‘sensitive relapse’ patients and ‘refractory relapse’ patients.

• Topotecan remains the standard-of-care for the treatment of second-line platinum-sensitive SCLC patients worldwide.

• Amrubicin is a valid alternative to topotecan but it is registered for administration in this setting only in Japan.

• To date, there are no targeted agents reporting results interesting enough to promote their clinical use in the next months.

• Immunotherapy is a new frontier for the management of cancers, including SCLC and with particularly regards to ‘refractory relapse’ patients. Preliminary results seem to be promising in pre-treated SCLC patients.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.