Regorafenib 40mg tablets

BackgroundRegorafenib is a standard second-line therapy for advanced hepatocellular carcinoma (HCC), but its efficacy as a monotherapy is limited. Combining regorafenib with immune checkpoint inhibitors (ICIs) may enhance antitumor activity through synergistic modulation of the tumor microenvironment. This study synthesizes real-world evidence from comparative cohorts by summarizing arm-level efficacy and safety outcomes reported for regorafenib plus ICIs and for regorafenib monotherapy.MethodsA systematic search of PubMed, Embase, The Cochrane Library, and Web of Science was conducted up to January 10, 2026, to identify comparative real-world studies. Outcomes were synthesized primarily at the arm level: ORR was pooled as a single-arm proportion, and mPFS/mOS were summarized using reported medians. Random-effects models and exploratory meta-regression were used to examine differences in pooled arm-level summaries across cohort types rather than within-study head-to-head comparative effect estimates.ResultsSix studies involving 921 patients were included. Because adjusted within-study comparative estimates were inconsistently reported, findings should be interpreted as non-comparative arm-level summaries. In arm-level pooling, cohorts receiving regorafenib plus ICIs had a higher pooled ORR (0.28, 95% CI: 0.23-0.32) than cohorts receiving regorafenib monotherapy (0.10, 95% CI: 0.06-0.14). The pooled mPFS summary was longer in the combination cohorts (7.34 months; 95% CI: 6.09-8.59) than in the monotherapy cohorts (3.97 months; 95% CI: 3.16-4.77). The pooled mOS summary was numerically longer with the combination (16.87 months) versus monotherapy (11.07 months). The incidence of grade ≥3 adverse events was broadly similar between cohort types.ConclusionIn this arm-level synthesis of real-world comparative cohorts, regorafenib plus ICIs was associated with numerically higher pooled response and longer pooled mPFS summaries than regorafenib monotherapy, while severe adverse event incidence appeared broadly similar across cohort types. Because these results are based on non-comparative pooled arm-level estimates and heterogeneous observational cohorts, they should be considered hypothesis-generating rather than definitive evidence of superiority. Prospective comparative trials and well-adjusted real-world analyses are needed to clarify comparative effectiveness and identify patients most likely to benefit.RegistrationPROSPERO CRD 420261290236.

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BackgroundTrifluridine/tipiracil (TAS-102) and regorafenib are approved and widely utilized as later-line treatment options for patients with metastatic colorectal cancer (mCRC). However, the optimal sequence between these agents remains unclear. We conducted a systematic review and meta-analysis to compare the efficacy and safety of two treatment sequences: TAS-102 followed by regorafenib (TR) versus regorafenib followed by TAS-102 (RT) in patients with mCRC who had previously failed chemotherapy.MethodsThis study was registered with PROSPERO (CRD42024622437). We systematically searched six databases (PubMed, Scopus, CINAHL, ScienceDirect, medRXiv, and OpenGrey) up to June 1, 2025. Risk of bias was assessed using the ROBINS-I tool. Pooled estimates with 95% confidence intervals (CIs) were calculated using a random-effects model. For studies lacking hazard ratios (HRs), we estimated the HRs using the ratio of median survival times. Publication bias was evaluated with a funnel plot.ResultsThirteen observational studies with moderate to critical risk of bias were included. No significant difference was found in overall survival (OS) (HR =1.04, 95% CI: 0.86-1.25, I2=72%) or progression-free survival (PFS) (HR =1.34, 95% CI: 0.77-2.34, I2=92%) between the TR and RT groups. The RT group had a higher disease control rate (DCR) (33.1% vs. 28.0%) and tended to have more adverse events (AEs).ConclusionsOS and PFS outcomes were comparable between patients treated with TAS-102 followed by regorafenib and those receiving the reverse sequence. Although the RT group was associated with a slightly higher DCR, this was accompanied by a trend toward increased AEs.

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Objectives: To evaluate and indirectly compare overall survival (OS) and safety of regorafenib, fruquintinib, and trifluridine/tipiracil (TAS-102) monotherapy in refractory metastatic colorectal cancer (mCRC) beyond the third line. Methods: A systematic review and meta-analysis of phase II/III randomized controlled trials was conducted according to PRISMA guidelines. PubMed/MEDLINE, Embase, and Cochrane CENTRAL were searched from inception. Eligible studies included patients with mCRC previously treated with standard chemotherapy and biologic agents, receiving regorafenib, fruquintinib, or TAS-102 as monotherapy in the fourth line or later. OS data were reconstructed from published Kaplan-Meier curves. Pooled median and mean OS were estimated using a random-effects model, and heterogeneity was assessed using the I2 statistic. Safety outcomes were descriptively summarized. Results: Four RCTs were included. The pooled median OS was 7.83 months (95% CI: 6.98-8.80), and the pooled mean OS was 8.90 months (95% CI: 8.00-9.81), with no heterogeneity (I2 = 0%). Survival gains versus placebo ranged from 1.4 to 2.6 months. Survival curves largely overlapped, with differences below one month. Safety was consistent with known profiles. Conclusions: These agents provide comparable efficacy with modest survival benefit in late-line mCRC, highlighting the need for improved strategies and better treatment sequencing.

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BackgroundThe efficacy of second-line tyrosine kinase inhibitors (TKIs) after first-line immunotherapy-based (IO) treatment in advanced hepatocellular carcinoma (HCC) is not well-established.MethodsA systematic search was conducted to identify studies reporting outcomes with second-line TKIs after progression on first-line IO-based treatment. This reconstructed individual patient data (IPD) meta-analysis used survival data reconstructed from published Kaplan-Meier curves. Studies presenting or combining third-line-or-beyond data were excluded. Overall survival (OS) (primary endpoint) and progression-free survival (PFS) were analyzed using restricted mean survival time (RMST), and random-effects univariable and adjusted meta-regression analyses were performed to account for heterogeneity and potential confounding.ResultsA total of 1,663 patients (16 studies) were included (sorafenib [n = 769], lenvatinib [n = 691], regorafenib [n = 105], and cabozantinib [n = 98]). Most patients received atezolizumab-bevacizumab in the first line. Cabozantinib was excluded from primary analyses as 83.7% of the data were derived from a single study, and baseline characteristics data were limited. The regorafenib group had significantly more Child-Pugh A and less macrovascular invasion. Median OS of all patients was 9.8 months (95% CI 9.4-10.2). The 12-month OS was significantly longer with lenvatinib or regorafenib compared with sorafenib (ΔRMST, 1.49 months [95% CI 1.10-1.88], p ConclusionsIn this reconstructed IPD meta-analysis of predominantly retrospective studies, survival outcomes with second-line TKIs after IO-based therapy were heterogeneous. Lenvatinib and regorafenib showed consistent survival compared with sorafenib; however, findings are exploratory, limited by the observational nature of the data and residual confounding. Prospective studies are needed to define optimal post-immunotherapy sequencing strategies.Impact and implicationsThis study addresses a critical evidence gap in advanced hepatocellular carcinoma by synthesizing available real-world data on second-line TKIs after IO-based first-line treatment, using reconstructed individual patient data and restricted mean survival time to accommodate non-proportional hazards and heterogeneous follow-up. The findings should not be interpreted as a recommendation for any specific TKI. Instead, they describe current survival patterns across heterogeneous retrospective cohorts and underscore the absence of robust comparative evidence in the post-immunotherapy setting. The results are relevant for clinicians and multidisciplinary teams caring for patients who progress after immunotherapy, as they may help contextualize expectations, support shared decision-making with patients and caregivers, and highlight areas of doubt in routine practice. This work highlights the unmet need for prospective randomized trials and high-quality real-world registries to define optimal treatment sequencing, inform regulatory decisions, and ensure equitable access to evidence-based therapies.Systematic review registrationThis study was registered with PROSPERO (Protocol No.: CRD420251133124).

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Background/Objectives: Standard treatment of multiply relapsed Ewing sarcoma remains to be established. Recent studies evaluating tyrosine kinase inhibitors (TKIs) with anti-angiogenic properties have shown encouraging results. Therefore, we conducted a systematic review and meta-analysis to explore the efficacy and safety of TKIs in patients with Ewing sarcoma. Methods: We comprehensively searched PubMed, Embase, and Cochrane databases for clinical trials (CTs) and cohort studies assessing TKIs in the treatment of advanced Ewing sarcoma patients who received at least one prior line of therapy. The main outcome was objective response rate (ORR). All analyses were conducted using R software (v.4.2.2), employing random effects models with 95% confidence intervals (CIs). Results: We included 14 studies (seven phase II CT and seven retrospective cohorts), comprising 257 patients. The following TKIs were evaluated: cabozantinib, regorafenib, apatinib, anlotinib, sorafenib, lenvatinib, sunitinib, fruquintinib, and imatinib. In a pooled analysis of all Ewing sarcoma patients treated with TKIs, the ORR was 23% (95% CI, 11.2-37.1%) and the DCR was 61.1% (95% CI, 47.3-74.2%). Responses were numerically higher but statistically nonsignificant between clinical trials and real-world studies. The analysis including only single-agent TKIs showed better responses for anlotinib and apatinib, yet these drugs are not available in Western countries. Among the FDA-approved TKIs, superior outcomes were noted with single-agent cabozantinib. (ORR: 21.6%) and regorafenib (ORR: 11.3%). Several studies did not report toxicity data exclusively for Ewing sarcoma patients; thus, conclusions about toxicity are mostly based on the general population of studies and may not be fully representative of Ewing sarcoma patients. Conclusions: Anti-angiogenic TKIs have shown important anti-tumoral activity in patients with Ewing sarcoma. Efficacy was consistently seen in both clinical trials and real-world studies. Nonetheless, there are important differences in study design and population that may limit our interpretation of efficacy and toxicity findings.

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Objectives The aim of this systematic review is comparing the efficacy and safety of traditional chemotherapy with targeted therapy in managing lung cancer, colorectal cancer (CRC), and hepatocellular carcinoma (HCC). Materials and Methods Article search was conducted on PubMed, Cochrane, Google Scholar, EMBASE, and Web of Science for three weeks, including published or unpublished randomized articles comparing the two treatment modalities in adults. Non-randomized trials or trials comparing one therapy with a placebo or another in the same class were excluded. Eighteen articles were selected and assessed for their bias risk by the Cochrane Collaboration tool, demonstrating a low overall risk of bias. Their methodological quality was evaluated as high by Jadad Scale. Results Results were synthesized narratively, finding that in non-small cell lung cancer (NSCLC), targeted therapy of either afatinib or erlotinib significantly enhanced overall survival (OS) (LUX-Lung 3: p = 0·0015 ; LUX-Lung 6: p = 0·023 ) and progression-free survival (PFS) ( p < 0.0001 ), respectively, in comparison to chemotherapy with less incidence of grade 3 or greater adverse events. The efficacy of bevacizumab with chemotherapy showed a contradiction in enhancing OS in two studies conducted in the context of metastatic colorectal cancer (mCRC) with 10% more hypertension and diarrhea occurrence. Targeted therapy of aflibercept and regorafenib showed promising OS ( p = 0.0032 and p = 0.0052 , respectively) and PFS ( p < 0.0001 for both agents) results for refractory mCRC. Concerning HCC, sorafenib alone demonstrated OS benefits ( p < 0.001 ), while regorafenib and nivolumab were safe alternatives upon progression. Lenvatinib and pembrolizumab had promising results in unresectable HCC. Conclusion This paper was limited by exempting articles lacking a direct comparison with chemotherapy in HCC and for not conducting a meta-analysis of its results. It suggested validating targeted therapy in NSCLC and investigating gained resistance and optimal sequencing with it.

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BackgroundGuideline-recommended nontargeted systemic therapies for previously treated metastatic colorectal cancer (mCRC) include regorafenib, trifluridine/tipiracil, and fruquintinib, but no consensus exists on the definition of clinically meaningful improvements for later-line mCRC treatments.Materials and methodsTrials were identified from systematic searches in MEDLINE, Embase, and the Cochrane Library. Meta-analyses were performed to characterize overall survival (OS) and progression-free survival (PFS) improvements with systemic therapy vs placebo in previously treated mCRC. Meta-analyses were conducted using fixed-effect and random-effects (RE) frequentist models of difference in medians, hazard ratios (HRs), and 12-month restricted mean survival time (RMST).ResultsSix randomized, placebo-controlled, phase III trials of 3277 patients comparing oral systemic monotherapies with placebo were analyzed. Using the RE model, the meta-analyzed OS estimate for oral systemic monotherapy vs placebo was 1.86 months (95% confidence interval [CI], 1.30-2.42) for the difference in medians, 0.69 (95% CI, 0.64-0.76) for HRs, and 1.25 months (95% CI, 0.69-1.82) for the difference in 12-month RMST. For PFS, meta-analyzed median improvement was 0.97 months (95% CI, 0.28-1.66), HR was 0.38 (95% CI, 0.30-0.47), and 12-month RMST difference was 1.90 months (95% CI, 1.41-2.39). Sensitivity analyses, excluding the FRESCO-2 trial due to prior treatment differences, confirmed the primary meta-analysis results.ConclusionWhen assessing the clinical benefit of later-line mCRC treatments, the broad clinical picture, including individualized treatment goals, should be evaluated. Considering multiple survival measures in the later-line mCRC context, an incremental survival improvement with oral systemic monotherapy vs no active therapy is clinically meaningful.

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BackgroundRegorafenib alone has shown limited efficacy in some cases of colorectal cancer (CRC), while the use of programmed cell death protein 1 (PD-1)/programmed cell death-ligand 1 (PD-L1) inhibitors is becoming increasingly common in cancer treatment. Previous studies have indicated significant benefits of combining regorafenib with PD-1/PD-L1 inhibitors in patients with advanced or metastatic CRC. This study aimed to evaluate the efficacy and outcomes of combining regorafenib with PD-1/PD-L1 inhibitors in patients with advanced or metastatic CRC.MethodsWe systematically retrieved clinical trials from PubMed and Embase up to August 1, 2023. The quality of eligible clinical trials was assessed using the methodological index for non-randomized studies and the JBI critical appraisal checklist for case eeries. Efficacy metrics, such as objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), and median overall survival, were analyzed using STATA version 15.1, with results presented as 95% confidence intervals. Heterogeneity was assessed using the chi-square Q test and I² statistic, with I² > 50% indicating high heterogeneity, which was addressed using a random effects model.ResultsFourteen studies were included in this meta-analysis. The pooled ORR, DCR, and mPFS were 7%, 54%, and 2.99 months, respectively. Subgroup analysis revealed that for patients with liver metastasis (LM), the pooled ORR was 6%, DCR was 47%, and mPFS was 1.99 months. In contrast, for patients without LM, the pooled ORR was 21%, DCR was 61%, and mPFS was 3.48 months.ConclusionThese results indicate that combination therapy is more effective in patients without LM than in those with LM. This suggests that regorafenib plus PD-1/PD-L1 inhibitors may be a more suitable option for patients without liver metastases.

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