Introduction: Recent studies have suggested enhanced therapeutic effects of subsequent chemotherapy after immune checkpoint inhibitor (ICI) treatment, highlighting the importance of subsequent treatment selection. Nanoparticle albumin-bound paclitaxel (nab-PTX) is commonly used in subsequent chemotherapies; however, its efficacy as a subsequent treatment after ICI treatment has not been reported. Methods: We retrospectively evaluated the efficacy and safety of nab-PTX using two prospective studies that we previously reported. The first study evaluated the efficacy and safety of nab-PTX as a second-line treatment after the failure of the first-line cytotoxic chemotherapy, excluding ICI (study 1; n = 32), and the other as a subsequent treatment after failure of ICI treatment, regardless of treatment line (study 2; n = 29). Results: The objective response rate was significantly higher in study 2 {55.2% (95% confidence interval [CI]: 28.1–79.6)} than in study 1 (28.1% [95% CI: 13.7–46.7]) (p = 0.04). Although the disease control rate was slightly higher in study 2 (86.2% [95% CI: 65.9–97.0]) than in study 1 (71.9% [95% CI: 53.3–86.3]), there was no significant difference (p = 0.2). The median progression-free survival was significantly longer in study 2 than in study 1 (3.9 months [95% CI: 2.0–5.5] in study 1 vs. 5.6 months [95% CI: 3.0–12.8] in study 2; hazard ratio [HR]: 0.46 [95% CI: 0.27–0.81], p = 0.006). The median overall survival was slightly longer in study 2 despite the greater number of patients who received nab-PTX in late treatment line, but there was no significant difference between study 1 and study 2 (10.9 months [95% CI: 5.1–16.8] in study 1 vs. 11.9 months [95% CI: 7.6–24.8] in study 2; HR: 0.77 [95% CI: 0.46–1.31], p = 0.34). Safety profiles did not differ between the patients in studies 1 and 2. Conclusion: Nab-PTX monotherapy may be an effective subsequent treatment option after ICI treatment.

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