DISCUSSION
NSCLC, pneumonia
ADVERSE EVENTS, PNEUMONIA, NSCLC
This prospective Phase 2 study evaluated the efficacy and safety of nab‐paclitaxel therapy in patients with advanced NSCLC treated with ICI alone or in combination with chemotherapy and ICI as a pretreatment and demonstrated an ORR that was higher than expected, with acceptable safety. The ORR in this study (55.2%) was higher compared to the ORR (28.1%) that was previously reported for nab‐paclitaxel as a second‐line therapy for patients with NSCLC who had not received ICI as prior therapy.Several retrospective studies have reported improved efficacy of chemotherapy after immunotherapy for NSCLC.In the present study, the long‐term response of 2 years or longer was observed in 13.3% patients. Long‐term responses are generally not observed with single‐agent anticancer therapy and are often observed in the course of immunotherapy. Furthermore, long‐term responses may be a corollary of the continued efficacy of immunotherapy. In fact, a single dose of PD‐1 antibody, binding peripheral blood T cells, can persist for approximately 5 months and may continue to be effective during the next treatment.Pretreatment with ICI might exacerbate the adverse events of the subsequent chemotherapy, and it was vital to evaluate the safety of treatment. Moreover, previous reports on single‐agent chemotherapy with nab‐paclitaxel for patients with NSCLC have reported a median number of treatment cycles of 3–5,Although these results were clinically relevant, the study has several research limitations. First, the sample size was relatively small, and caution must be exercised regarding survival probability and frequency of adverse events. A Phase 3 randomized trial is needed to accurately validate the results of this study. However, since designing such a trial is difficult, it is necessary to validate the results in a Phase 2 trial such as the present study or in a retrospective trial with a large number of cases. Second, nab‐paclitaxel was used in this study, but further studies are needed to determine whether other agents can provide similar efficacy. Third, because only ICI monotherapy was approved in Japan during most of the study period, chemoimmunotherapy was administered as pretreatment in only a few cases in the current study. Therefore, whether nab‐paclitaxel monotherapy after chemoimmunotherapy is as effective as the present results indicate needs to be verified in the future.In conclusion, this is the first prospective study to evaluate the effect of nab‐paclitaxel monotherapy after ICI treatment failure in patients with advanced NSCLC. The ORR of nab‐paclitaxel was clearly better than those of standard single‐agent chemotherapies, and a durable response lasting more than 2 years was observed in 13% of all cases. These results may demonstrate that ICI treatment enhances the effect of subsequent chemotherapy. The adverse events of nab‐paclitaxel immediately after ICI treatment are similar to those reported for nab‐paclitaxel therapy; however, the possible increase in the incidence of drug‐induced pneumonia should be considered cautiously. Although further studies are required, we suggest that nab‐paclitaxel after ICI is an appropriate treatment for advanced NSCLC.