Dataset Information

Efficacy and Safety of Docetaxel and Sodium Cantharidinate Combination vs. Either Agent Alone as Second-Line Treatment for Advanced/Metastatic NSCLC With Wild-Type or Unknown EGFR Status: An Open-Label, Randomized Controlled, Prospective, Multi-Center Phase III Trial (Cando-L1).

ABSTRACT: Second-line treatment options for advanced/metastatic non-small cell lung cancer (NSCLC) patients are limited. We aimed to evaluate the efficacy and safety of docetaxel/sodium cantharidinate combination vs. either agent alone as second-line treatment for advanced/metastatic NSCLC patients with wild-type or unknown EGFR status. A randomized, open-label, phase III study was performed at 12 institutions. Patients with failure of first-line platinum regimens were randomized to receive either single-agent sodium cantharivsdinate (SCA) or single-agent docetaxel (DOX) or docetaxel/sodium cantharidinate combination (CON). The primary endpoints were centrally confirmed progression-free survival (PFS) and overall survival (OS). The secondary endpoints were objective response rate (ORR), disease control rate (DCR), quality of life (QoL) and toxicity. A total of 148 patients were enrolled in our study between October 2016 and March 2020. After a median follow-up time of 8.02 months, no significant difference was observed among the three groups in ORR (SCA vs. DOX vs. CON: 6.00% vs. 8.33% vs. 10.00%, respectively; p=0.814) and DCR (74.00% vs. 52.00% vs. 62.50%, respectively; p=0.080). In additional, the mOS was significantly higher in the CON group, compared with the single-agent groups (7.27 vs. 5.03 vs. 9.83 months, respectively; p=0.035), while no significant differences were observed in terms of PFS (2.7 vs. 2.9 vs. 3.1 months, respectively; p=0.740). There was no significant difference in the baseline QoL scores between the three groups (p>0.05); after treatment, life quality in SCA and CON group was significantly better than that in the DOX group (p<0.05). Furthermore, the incidence of adverse events (AEs) in the SCA group was significantly lower (46.00 vs. 79.17 vs. 25.00%, respectively; p=0.038) and the incidence of grade ≥3 AEs was also significantly lower in the SCA group compared with the DOX and CON groups (10.00 vs. 82.00 vs. 30.00%, respectively; p=0.042). Single-agent SCA and single-agent DOX has similar therapeutic efficacy in the second-line treatment of advanced/metastatic NSCLC with wild-type or unknown EGFR status, but single-agent SCA has fewer AEs and better QoL. Also, SCA plus DOX can significantly improve OS and exerted a significant synergistic effect, with good safety and tolerance profile.

SUBMITTER: Wu L

PROVIDER: S-EPMC8715707 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundFrequent failures observed in some trials comparing the efficacy and safety of osimertinib plus bevacizumab to osimertinib monotherapy in advanced non-small-cell lung cancer (NSCLC) with epidermal growth factor receptor (EGFR) alterations have brought questions.ObjectivesTo evaluate the efficacy and safety of these two treatment regimens in advanced NSCLC patients harboring EGFR mutations.DesignThis study is a systematic review and meta-analysis.Data sources and methodsPubMed, Embase, Cochrane Library, Web of Science, CNKI, Wanfang, and VIP databases were extensively searched for relevant randomized controlled trials (RCTs) on 14 May 2023. Two researchers independently screened the literature, assessed quality, and extracted data. The primary outcomes were progression-free survival (PFS), overall survival (OS), and objective response rate (ORR). The secondary outcomes were adverse events (AEs) and PFS stratified by patients' characteristics. STATA 17.0 software (StataCorp LLC, USA) was adopted for meta-analysis.ResultsA total of four RCTs involving 390 patients were included. Overall, the risk of bias across the studies was moderate to low. Pooled results showed that compared to osimertinib alone, the addition of bevacizumab to osimertinib failed to show prolongation of PFS [hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.78-1.27], OS (HR = 1.01, 95% CI: 0.73-1.41), or improvement of the ORR (risk ratio = 1.12, 95% CI: 0.90-1.38), while an increased incidence of some AEs was observed, such as nausea, oral mucositis, hypertension, and proteinuria. Notably, combination treatment did significantly prolong the PFS in the subset of smokers (HR = 0.64, 95% CI: 0.44-0.94). A mild trend toward PFS benefit under the combined regimen was also noted in patients with brain metastases and first-line treatment, though not reaching statistical significance.ConclusionBased on the available evidence, the addition of bevacizumab to osimertinib could not provide additional survival benefits with higher but manageable toxicity for EGFR-mutant NSCLC patients. Osimertinib monotherapy remains the prioritized treatment. Further investigation is warranted.

Project description:BackgroundDespite disappointing outcomes from immuno-monotherapy, studies reported that NSCLC patients with EGFR mutation may possibly benefit from combined immunotherapy. Whether the response to prior EGFR-TKI has association with the outcomes of subsequent immunotherapy remains unclear.Patients and methodsAdvanced NSCLC patients with resistance to EGFR-TKIs and received ICI treatment from January 2016 to June 2019 were retrospectively analyzed. Single cell sequencing and flow cytometry were conducted to explore the difference of cell components in tumor microenvironments (TME). A 1:3 matched case-control study was conducted to compare the clinical effects of combined immunotherapy with standard chemotherapy as second-line treatment.ResultsFifty-eight patients treated with anti-PD-1/PD-L1 based immunotherapy behind EGFR-TKI treatment were enrolled. Correlation analysis showed TKI-PFS had a significantly negative association with corresponding IO-PFS (r = -0.35, p = 0.006). TKI-PFS cutoff 10 months had the most significant predictive function for posterior immunotherapy and was validated to be an independent predictor by uni- and multivariate analyses. Kaplan-Meier analysis showed that patients with TKI-PFS less than 10 months had significantly prolonged IO-PFS and higher ORR than those with long (median PFS, 15.1 vs 3.8 months; HR, 0.26, p = 0.0002; ORR, 31.8 versus 10%, p = 0.04). Single cell RNA-seq revealed that the cell components were varied among patients after treatment with EGFR-TKI. Patients with short TKI-PFS demonstrated a relatively higher proportion of CD8 effector cells and lower ratio of M2 like macrophage to M1 like macrophages, which was validated by flow cytometry. Case-control study demonstrated that combined immunotherapy achieved significantly longer PFS (HR, 0.51, 95% CI: 0.31-0.85, p = 0.02), longer OS (HR, 0.48, 95% CI: 0.26-0.89, p = 0.05) and higher ORR (33.3 vs 10.0%, p = 0.02) than traditional chemotherapy for patients with short TKI-PFS.ConclusionPatients with short TKI-PFS conferred better response to immunotherapy than those with long. The status of TME were different among those two populations. Combined ICI treatment could promisingly be a better choice than classical chemotherapy in second-line setting for patients with short TKI-PFS and no T790M mutation. Underlying mechanisms need to be further explored.

Dataset Information

Efficacy and Safety of Docetaxel and Sodium Cantharidinate Combination vs. Either Agent Alone as Second-Line Treatment for Advanced/Metastatic NSCLC With Wild-Type or Unknown EGFR Status: An Open-Label, Randomized Controlled, Prospective, Multi-Center Phase III Trial (Cando-L1).

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