Small cell lung cancer (SCLC) is a fatal disease that has not seen new drug approvals for the last 17 years. Considering the relative success of ‘immune checkpoint inhibitors’ in non-small cell lung cancer (NSCLC), it is not surprising that several abstracts recently presented at the 2015 American Society of Clinical Oncology (ASCO) annual meeting were devoted to clinical trials testing these trendy, immune system-boosting drugs in people with SCLC.
In the Keynote-028 trial, pembrolizumab (Keytruda) was given to patients with relapsed SCLC whose tumors tested positive for the presence of a protein called PD-L1. Seven of 20 patients (35%) responded, including one patient who achieved disease stabilization. More than half had an adverse reaction (side effect), but these were serious in only 10% of the patients.
Nivolumab (Opdivo) was tested in the CheckMate-032 study. It was given to SCLC patients who had already been heavily treated with other drugs, regardless of the results of PD-L1 testing. It was given either alone or with ipilimumab (Yervoy). Eighteen percent of patients in the Opdivo-only group responded to the drug, and 36% of patients responded to the combination of drugs.
Aside from the immunotherapy presentations, two other SCLC presentations at ASCO garnered attention. One of them reported on the activity of an investigational drug called IMMU-132 (aka sacituzumab govitecan) in patients with relapsed SCLC. IMMU-132 is an antibody-drug conjugate, wherein the antibody part of the drug binds to a protein on cancer cells called TROP-2. The antibody part is linked to the active form of the drug irinotecan, SN-38. Of 19 SCLC patients treated, 26% had partial responses, and another 27% had stabilization of disease—very impressive rates for relapsed SCLC.
The other notable presentation in the otherwise not overly impressive lineup of SCLC reports discussed a drug called PM1183. PM1183, (aka lurbinectedin) had previously been shown to kill cancer cells by suppressing transcription and inducing DNA breaks. In the present study, it was given together with the chemotherapy drug doxorubicin. The outcomes for patients who had previously responded to platinum-containing treatment (meaning that they were disease-free for more than 3 months) were great: they all responded to PM1183 and doxorubicin, and 18% of them even had complete responses (no more signs of a tumor). Patients who were resistant to platinum-containing treatments (meaning that they were disease-free for less than 3 months after treatment) showed a lower response rate of 30%— still unprecedented for resistant SCLC.