2432 - Retrospective comparative study of the efficacy and safety in docetaxel and ramucirumab combination chemotherapy with or without previous immune checkpoint inhibitor treatment.

Background

Salvage chemotherapy after immune checkpoint inhibitor (ICI) treatment has been reported to increase the antitumor effect. There are also some reports that activation of vascular endothelial growth factor (VEGF) / its receptor (VEGFR) signal is one of the ICI resistant mechanism, and that combination therapy of VEGF / VEGFR inhibitor and ICI had synergistic effect. In ICI pretreated patients, docetaxel and ramucirumab combination therapy (DOC+RAM) may be more effective. In order to verify this hypothesis, the retrospective observation study was conducted.

Methods

From June 2013 to July 2018, in 39 patients with advanced / recurrent non-small cell lung cancer who underwent DOC+RAM therapy at our hospital the efficacy and safety were analysed based on the presence (pre-ICI+) or absence (pre-ICI-) of ICI pretreatment history.

Results

Of the 39 patients treated with DOC+RAM, 18 (pre-ICI+: 46%) patients had been pretreated with ICI. The characteristics (pre-ICI+/ pre-ICI-) were as follows; median age was 67/65 years, median treatment line was 3/3, ECOG PS:0,1 was 94%/86%, 83%/48% were male, 72%/95% had adenocarcinoma, and 89%/67% were smokers, PD-L1status ≧50% was 6%/5%, 11%/38% had EGFR mutation. The ORRs for DOC+RAM in pre-ICI+ and pre-ICI- were 38.9% vs. 19.0%, respectively (p = 0.29). Median progression free survival was 5.7 vs. 2.3 months (hazard ratio (HR), 0.36; 95% confidential interval [CI], 0.16-0.80). Median overall survival was 13.8 vs. 10.5 months (HR, 0.41; 95% [CI], 0.16-1.04). Because of adverse events, nine patients (50%) in pre-ICI+ group and two patients (9.5%) in pre-ICI- group discontinued DOC+RAM therapy. Adverse events such as fever (50%/38%), myalgia (39%/9.5%), arthritis (33%/4.8%), pleural effusion (22%/4.8%) and pneumonitis (17%/4.8%) tended to be more frequent in pre-ICI+ group. There were no grade 5 AEs.

Conclusions

In this study, statistically significant prolongation of PFS, the tendency of tumor regression improvement and OS prolongation achieved by DOC + RAM, and the concern of increased toxicity were shown in pre-ICI+ patients.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Daijiro Harada.

Funding

Has not received any funding.

Disclosure

D. Harada: Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K.; Research grant / Funding (institution): Novartis International AG; Research grant / Funding (institution): Kissei Pharmaceutical Co., Ltd; Research grant / Funding (institution): Takeda Pharmaceutical Company Limited.; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): Bristol-Myers Squibb Company; Honoraria (self): Kyowa Hakko Kirin Co., Ltd.; Honoraria (self): Eli Lilly and Company Nyse: LLY; Honoraria (self): MSD K.K. ; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self): Nippon Boehringer Ingelheim Co ., Ltd. T. Kozuki: Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): AstraZeneca K.K; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan K.K.; Honoraria (self): Taiho Pharmaceutical Co., Ltd.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers K.K; Honoraria (self): Ono Pharmaceutical Co., Ltd.; Honoraria (self): MSD K.K; Honoraria (self), Research grant / Funding (institution): Pfizer; Honoraria (self): Kyowa Hakko Kirin Co., Ltd; Honoraria (self): Nippon Beohringer Ingelheim Co., Ltd.; Honoraria (self): Nippon-Kayaku Co.; Research grant / Funding (institution): Merck Serono. N. Nogami: Honoraria (self): Astellas Pharma; Honoraria (self): AstraZeneca; Honoraria (self): Ono Pharmaceutical; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Chugai Pharmaceutical; Honoraria (self): Eli Lilly; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pfizer. All other authors have declared no conflicts of interest.