Conversion of Platinum-Etoposide-Resistant to Sensitive SCLC after Treatment with the Epi-Immunotherapeutic RRx-001: A Case Report.

Background: The response to first-line platinum doublets (cisplatin/etoposide) in small-cell lung cancer (SCLC) predicts the probability of subsequent response to second-line therapy. In general, the longer-lived the responses in first line, the better the outcome in second line, with the opposite prognosis for shorter-lived responses. Resistant SCLC is defined as relapse within 90 days of platinum-doublet treatment, and predictably correlates with shortened survival compared with sensitive disease, defined as relapse after 90 days.

Case Report: We present a patient with platinum-resistant SCLC that was rechallenged with cisplatin/etoposide in the context of the clinical trial TRIPLE THREAT (NCT02489903) after treatment with, and progression on, the resistance-reversing anticancer agent RRx-001.

Conclusion: The prolonged partial response of this platinum-resistant SCLC to reintroduced carboplatin/etoposide after RRx-001 belies and contradicts the prevailing orthodoxy in oncology that rechallenge with chemotherapy after the emergence of resistance is an exercise in futility and risk, which potentially exposes patients to toxicity without benefit.