Oncology · Medical Literature
Docetaxel plus ramucirumab immediately after immunotherapy in advanced NSCLC: A phase II study (DRUN).
Abstract
Docetaxel plus ramucirumab is a standard second-line treatment for advanced non-small cell lung cancer (NSCLC). Prior immunotherapy has been suggested to potentially affect the efficacy of subsequent docetaxel plus ramucirumab, but prospective evidence is limited. This multicenter, single-arm, phase II study enrolled patients with advanced NSCLC. Eligible patients had experienced disease progression following a prior immune checkpoint inhibitor (ICI)-containing regimen. Patients received docetaxel 60 mg/m2 and ramucirumab 10 mg/kg every 3 weeks. The primary endpoint was objective response rate (ORR). Secondary endpoints included progression-free survival (PFS), overall survival (OS), disease control rate (DCR), and safety. This study was registered in the Japan Registry of Clinical Trials (jRCT1051190091). Between January 8, 2020, and January 7, 2024,We evaluated 33 patients for efficacy and safety. The median age was 69 years, and 26 patients (79%) had an Eastern Cooperative Oncology Group performance status of 1. The ORR was 33.3% (90% confidence interval [CI], 19.9-49.1), and the DCR was 90.9% (90% CI, 78.1-97.5). The median PFS and OS were 4.9 months (95% CI, 4.4-6.2) and 11.8 months (95% CI, 9.8-18.8), respectively. No new safety signals were observed. Patients who had responded to prior ICI-containing therapy had longer PFS than those who had not responded (hazard ratio, 0.34; 95% CI, 0.14-0.76). Although the primary endpoint was not met, docetaxel plus ramucirumab demonstrated antitumor activity consistent with previous reports and manageable safety in the post-ICI setting. Efficacy appeared more pronounced in patients with prior response to ICI-containing therapy.
Clinical relevance
In patients with advanced NSCLC who have progressed on a prior ICI-containing regimen, does docetaxel plus ramucirumab administered immediately after immunotherapy achieve an objective response rate sufficient to demonstrate meaningful antitumor activity compared to a predefined historical threshold? __SNAPSHOT__ {"studyDesign":"Multicenter, open-label, single-arm, phase II trial","setting":"Japan; multicenter academic setting (registered in the Japan Registry of Clinical Trials, jRCT1051190091)","sampleSize":"n=33 (single arm, all evaluated for efficacy and safety)","population":"Adults aged ≥20 years with advanced (stage III/IV or recurrent) NSCLC, ECOG PS 0–1, prior platinum-based chemotherapy and ICI (concurrent or sequential), disease progression during or after an ICI-containing regimen, ≤2 prior lines of systemic therapy (excluding targeted therapies for oncogenic driver alterations); median age 69 years, 79% with ECOG PS 1","intervention":"Docetaxel 60 mg/m² plus ramucirumab 10 mg/kg IV every 3 weeks, administered immediately after progression on prior ICI-containing therapy","comparator":"Not applicable (single-arm study); efficacy assessed against a predefined threshold ORR of 25% derived from the REVEL trial ORR of 23%","primaryOutcome":"Objective response rate (ORR), defined as proportion of patients achieving confirmed complete or partial response by investigator assessment per RECIST","followUp":"Enrollment January 8, 2020 to January 7, 2024; exact median follow-up duration not reported in available abstract","fundingSource":"Not reported in available abstract"}
Key findings
Among 33 evaluable patients, 11 achieved partial response and 0 achieved complete response, yielding an ORR of 33.3% (90% CI 19.9–49.1%). The disease control rate (DCR) was 90.9% (90% CI 78.1–97.5%), with 19 additional patients achieving stable disease. The primary endpoint was formally not met: the lower limit of the 90% CI for ORR (19.9%) did not exceed the predefined threshold ORR of 25%. Median PFS was 4.9 months (95% CI 4.4–6.2) and median OS was 11.8 months (95% CI 9.8–18.8). In an exploratory subgroup analysis, patients who had previously responded to ICI-containing therapy demonstrated significantly longer PFS compared with non-responders (HR 0.34, 95% CI 0.14–0.76; p<0.01 per secondary source). NNT and NNH are not calculable from the available data. The safety profile was consistent with known toxicities of the regimen; no treatment-related deaths or new safety signals were reported. Hematologic toxicities were common, managed in part with prophylactic PEG-G-CSF. Pneumonitis was identified as a clinically notable toxicity signal, observed exclusively in patients with a smoking history. Absolute rates of individual adverse events are not reported in the available abstract.
Practice implications
The DRUN trial provides prospective, multicenter evidence that docetaxel plus ramucirumab retains meaningful antitumor activity in the post-ICI setting, with an ORR of 33.3% and a DCR exceeding 90%—both numerically higher than historical REVEL data (ORR 23%) generated in an ICI-naïve population. Nevertheless, the study formally failed its primary endpoint because the lower bound of the 90% CI crossed the predefined 25% threshold, meaning the superiority hypothesis was not statistically confirmed in this small cohort. The median OS of 11.8 months compares favorably to the REVEL OS of 10.5 months and is consistent with other prospective datasets in the post-ICI setting (SCORPION: median PFS 6.5 months, OS 17.5 months). The most clinically actionable secondary finding is the exploratory PFS benefit in prior ICI responders (HR 0.34), suggesting that prior ICI responsiveness may be a useful clinical enrichment criterion for this regimen; however, this is hypothesis-generating only and was not a pre-specified powered endpoint. Patients with ECOG PS ≥2, active driver mutations receiving targeted therapy beyond the ≤2-line cap, and those with untreated brain metastases were not represented or were excluded, limiting direct generalizability. More than 80% of patients began treatment within 60 days of their last ICI dose, which defines the specific post-ICI timing context this data applies to. The pneumonitis signal in smokers warrants heightened vigilance when administering this doublet shortly after ICI exposure. IMPORTANT LIMITATION: This summary is based solely on the published abstract and secondary reporting; full-text data on individual toxicity rates, histological subgroups, driver mutation status distribution, and time-to-event curve censoring rates were not available for review. __LIMITATIONS__ Small sample size (n=33) substantially limits statistical power; the primary endpoint was not met and the study was not adequately powered to confirm superiority over the historical threshold,Single-arm design with no concurrent control; comparisons to REVEL or SCORPION are cross-trial and confounded by differences in era, patient selection, molecular genotypes, and geography,Entirely Japanese multicenter population limits generalizability to non-Asian patients and healthcare systems with different ICI exposure patterns and genetic backgrounds,Exploratory subgroup analysis of prior ICI responders vs. non-responders is hypothesis-generating only; not pre-specified as a powered endpoint and subject to selection bias,The predefined expected ORR of 45% (used for sample size calculation) was substantially higher than observed (33.3%), suggesting the power assumptions were optimistic,Follow-up duration and censoring rates in the OS analysis are not fully reported in the abstract, precluding assessment of OS estimate maturity,Docetaxel dose of 60 mg/m² (Japanese standard) differs from the 75 mg/m² used in REVEL and SCORPION, limiting direct cross-trial efficacy comparisons,Individual adverse event rates and grades are not reported in the available abstract, limiting toxicity characterization,Pneumonitis signal in smokers is based on a very small number of events; formal attribution to the regimen versus prior ICI-related pulmonary toxicity cannot be established from abstract data alone,Funding source not reported; potential for undisclosed conflicts of interest cannot be assessed __BOTTOM_LINE_CATEGORY__ confirmatory __BOTTOM_LINE__ The DRUN trial demonstrates that docetaxel plus ramucirumab is clinically active immediately after ICI progression in advanced NSCLC, with an ORR of 33.3% and DCR of 90.9%, although the predefined primary efficacy threshold was narrowly missed in this small single-arm study. The exploratory finding of substantially longer PFS in prior ICI responders (HR 0.34) is hypothesis-generating and warrants prospective validation as a potential selection strategy. This regimen remains a reasonable post-ICI salvage option consistent with current practice, but these results alone do not mandate a change in treatment selection algorithms pending larger confirmatory data.