Background: Lurbinectedin is a novel second-line option for refractory small-cell lung cancer. It is a synthetic alkaloid that functions by covalently binding to DNA and generates double-strand breaks, and disrupts DNA-protein interactions and RNA transcription. It is yet to be well established in the literature if the overall response rate (ORR) can predict progression-free survival (PFS) and/or overall survival (OS). This study aims to investigate the correlations between PFS, ORR, and OS in refractory small-cell lung cancer treated with lurbinectedin. Methods: PubMed, Google Scholar, and Clinicaltrials.gov databases were queried for randomized, phase 3 clinical trials, phase 2 trials, phase 1 trials with expansion cohorts, and retrospective and prospective studies. The criteria for eligibility included a clinical diagnosis of treatment-refractory small cell lung cancer, at least one prior line of therapy, articles in English, and lurbinectedin treatment. ORR, OS, and PFS data were extracted manually from the selected studies, and correlation analyses with Spearman’s rank correlation were performed. Results: Seventy-one articles and trials were identified. Seven articles, including 849 patients, met our criteria and were included for further analyses. OS and PFS were strongly correlated (rs = 0.9196, p-value = 0.02), whereas the correlation between OS and ORR was not statistically significant (rs = 0.6696, p-value = 0.20). Also, the correlation between ORR and PFS was not statistically significant (rS = 0.6785, p-value = 0.05419). Conclusions: There was a strong correlation between OS and PFS in studies investigating lurbinectedin use in patients with refractory small-cell lung cancer. There were no significant correlations between ORR and PFS/OS. We propose that PFS can be used as a surrogate for OS in studies involving lurbinectedin-treated refractory small-cell lung cancer, especially when the time to reach OS is protracted.