This column alerts SIR members to abstracts that may have an impact on their practice and how they converse with referring clinicians. If you would like to suggest abstracts you feel should be included, email us at gandhi@baptisthealth.net or suvranu.ganguli@bmc.org.
Arterial chemotherapy of oxaliplatin plus fluorouracil versus sorafenib in advanced hepatocellular carcinoma: A biomolecular exploratory, randomized, phase III trial (FOHAIC-1)
J Clin Oncol. 2021 Dec 14;JCO2101963. doi: 10.1200/JCO.21.01963.
Ning Lyu, Xun Wang, Ji-Bin Li, Jin-Fa Lai, Qi-Feng Chen, Shao-Long Li, Hai-Jing Deng, Meng He, Lu-Wen Mu, Ming Zhao
Purpose: Interventional hepatic arterial infusion chemotherapy of infusional fluorouracil, leucovorin and oxaliplatin (HAIC-FO) displayed an encouraging safety profile and antitumor activity in a previous Phase II trial and a propensity-score-matching study involving patients with locally advanced hepatocellular carcinoma (HCC).
Methods: In this open-label, Phase III trial, patients with advanced HCC, previously untreated with systemic therapy, were randomly assigned in a 1:1 ratio to receive HAIC-FO or sorafenib. The primary end point was overall survival (OS) in the intention-to-treat population. An exploratory model for predicting the efficacy of HAIC-FO on the basis of genomic sequencing was developed.
Results: Between May 2017 and May 2020, 262 patients were randomly assigned. The median tumor size was 11.2 cm (interquartile range, 8.5–13.7 cm). Macrovascular invasion was present in 65.6%, and the percentage of patients with > 50% tumor volume involvement of the liver and/or Vp-4 portal vein tumor thrombosis was 49.2%. At data cutoff (Oct. 31, 2020), median OS was 13.9 months for HAIC-FO and 8.2 for sorafenib (hazard ratio [HR] 0.408; 95% CI, 0.301 to 0.552; P < .001). Tumor downstaging occurred in 16 (12.3% of 130) patients receiving HAIC-FO, including 15 receiving curative surgery or ablation, and finally achieving a median OS of 20.8 months, with a 1-year OS rate of 93.8%. In high-risk subpopulations, OS was significantly longer with HAIC-FO than with sorafenib (10.8 months vs. 5.7 months; HR 0.343; 95% CI, 0.219 to 0.538; P < .001). A newly developed 15-mutant-gene prediction model identified 83% of patients with response to HAIC-FO. HAIC-FO responders had longer OS than HAIC-FO nonresponders (19.3 months vs. 10.6 months; HR 0.323; 95% CI, 0.186 to 0.560; P = .002).
Conclusion: HAIC-FO achieved better survival outcomes than sorafenib in advanced HCC, even in association with a high intrahepatic disease burden.
Radioembolization with chemotherapy for colorectal liver metastases: A randomized, open-label, international, multicenter, Phase III trial
J Clin Oncol. 2021 Dec 10;39(35):3897-3907. doi: 10.1200/JCO.21.01839. Epub 2021 Sep 20.
Mary F. Mulcahy, Armeen Mahvash, Marc Pracht, Amir H Montazeri, Steve Bandula, Robert C.G. Martin 2nd, Ken Herrmann, Ewan Brown, Darryl Zuckerman, Gregory Wilson, Tae-You Kim, Andrew Weaver, Paul Ross, William P. Harris, Janet Graham, Jamie Mills, Alfonso Yubero Esteban, Matthew S. Johnson, Constantinos T. Sofocleous, Siddharth A. Padia, Robert J. Lewandowski, Etienne Garin, Philip Sinclair, Riad Salem
Purpose: To study the impact of transarterial yttrium-90 radioembolization (TARE) in combination with second-line systemic chemotherapy for colorectal liver metastases (CLM).
Methods: In this international, multicenter, open-label Phase III trial, patients with CLM who progressed on oxaliplatin- or irinotecan-based first-line therapy were randomly assigned 1:1 to receive second-line chemotherapy with or without TARE. The two primary end points were progression-free survival (PFS) and hepatic PFS (hPFS), assessed by blinded independent central review. Random assignment was performed using a web- or voice-based system stratified by unilobar or bilobar disease, oxaliplatin- or irinotecan-based first-line chemotherapy, and KRAS mutation status.
Results: 428 patients from 95 centers in North America, Europe and Asia were randomly assigned to chemotherapy with or without TARE; this represents the intention-to-treat population and included 215 patients in the TARE plus chemotherapy group and 213 patients in the chemotherapy alone group. The hazard ratio (HR) for PFS was 0.69 (95% CI, 0.54 to 0.88; 1-sided P = .0013), with a median PFS of 8.0 (95% CI, 7.2 to 9.2) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. The HR for hPFS was 0.59 (95% CI, 0.46 to 0.77; 1-sided P < .0001), with a median hPFS of 9.1 (95% CI, 7.8 to 9.7) and 7.2 (95% CI, 5.7 to 7.6) months, respectively. Objective response rates were 34.0% (95% CI, 28.0 to 40.5) and 21.1% (95% CI, 16.2 to 27.1; 1-sided P = .0019) for the TARE and chemotherapy groups, respectively. Median overall survival was 14.0 (95% CI, 11.8 to 15.5) and 14.4 months (95% CI, 12.8 to 16.4; 1-sided P = .7229) with a HR of 1.07 (95% CI, 0.86 to 1.32) for TARE and chemotherapy groups, respectively. Grade 3 adverse events were reported more frequently with TARE (68.4% v 49.3%). Both groups received full chemotherapy dose intensity.
Conclusion: The addition of TARE to systemic therapy for second-line CLM led to longer PFS and hPFS. Further subset analyses are needed to better define the ideal patient population that would benefit from TARE.
Reduction in acute limb ischemia with rivaroxaban versus placebo in peripheral artery disease after lower extremity revascularization: Insights from VOYAGER PAD
Circulation. 2021 Dec 7;144(23):1831-1841. doi: 10.1161/CIRCULATION
Connie N. Hess, E. Sebastian Debus, Mark R. Nehler, Sonia S. Anand, Manesh R. Patel, Michael Szarek, Warren H. Capell, Judith Hsia, Joshua A. Beckman, Marianne Brodmann, Rafael Diaz, Peter Habertheuer, Nicholas J. Leeper, Richard J. Powell, Henrik Sillesen, Eva Muehlhofer, Scott D. Berkowitz, Lloyd P. Haskell, Rupert M. Bauersachs, Marc P Bonaca
Background: Patients with peripheral artery disease (PAD) are at heightened risk of acute limb ischemia (ALI), a thrombotic event associated with amputation, disability and mortality. Previous lower extremity revascularization (LER) is associated with increased ALI risk in chronic PAD. However, the pattern of risk, clinical correlates, and outcomes after ALI early after LER are not well-studied, and effective therapies to reduce ALI post-LER are lacking.
Methods: The VOYAGER PAD trial (Vascular outcomes study of ASA [acetylsalicylic acid] along with Rivaroxaban in endovascular or surgical limb revascularization for PAD; rNCT02504216) randomized patients with PAD undergoing LER to rivaroxaban 2.5 mg twice daily or placebo on a background of low-dose aspirin. The primary outcome was a composite of ALI, major amputation of vascular cause, myocardial infarction, ischemic stroke or cardiovascular death. ALI was prospectively ascertained and adjudicated by a blinded committee. The cumulative incidence of ALI was calculated using Kaplan-Meier estimates, and Cox proportional hazards models were used to generate hazard ratios and associated CIs. Analyses were performed as intention-to-treat.
Results: Among 6,564 patients followed for a median of 2.3 years, 382 (5.8%) had a total of 508 ALI events. In placebo patients, the 3-year cumulative incidence of ALI was 7.8%. After multivariable modeling, previous LER, baseline ankle-brachial index <0.50, surgical LER, and longer target lesion length were associated with increased risk of ALI. Incident ALI was associated with subsequent all-cause mortality (hazard ratio [HR], 2.59 [95% CI, 1.98-3.39]) and major amputation (HR, 24.87 [95% CI, 18.68-33.12]). Rivaroxaban reduced ALI relative to placebo by 33% (absolute risk reduction, 2.6% at 3 years; HR, 0.67 [95% CI, 0.55-0.82]; P=0.0001), with benefit starting early (HR, 0.45 [95% CI, 0.24-0.85]; P=0.0068 at 30 days). Benefit was present for severe ALI (associated with death, amputation, or prolonged hospitalization and intensive care unit stay, HR, 0.58 [95% CI, 0.40-0.83]; P=0.003) and regardless of LER type (surgical versus endovascular revascularization, P interaction=0.42) or clopidogrel use (P interaction=0.59).
Conclusions: After LER for symptomatic PAD, ALI is frequent, particularly early after LER, and is associated with poor prognosis. Low-dose rivaroxaban plus aspirin reduces ALI after LER, including ALI events associated with the most severe outcomes. The benefit of rivaroxaban for ALI appears early, continues over time, and is consistent regardless of revascularization approach or clopidogrel use.
Endoscopic cyanoacrylate injection versus balloon-occluded retrograde transvenous obliteration for prevention of gastric variceal bleeding: A randomized controlled trial
Hepatology. 2021 Oct;74(4):2074-2084. doi: 10.1002/hep.31718.
Xuefeng Luo, Tong Xiang, Junchao Wu, Xiaoze Wang, Yongjun Zhu, Xiaotan Xi, Yuling Yan, Jinlin Yang, Juan Carlos García-Pagán, Li Yang
Background and aims: The optimal treatment for gastric varices (GVs) is a topic that remains open for study. This study compared the efficacy and safety of endoscopic cyanoacrylate injection and balloon-occluded retrograde transvenous obliteration (BRTO) to prevent rebleeding in patients with cirrhosis and GVs after primary hemostasis.
Approach and results: Patients with cirrhosis and history of bleeding from gastroesophageal varices type 2 or isolated gastric varices type 1 were randomized to cyanoacrylate injection (n = 32) or BRTO treatment (n = 32). Primary outcomes were gastric variceal rebleeding or all-cause rebleeding. Patient characteristics were well balanced between two groups. Mean follow-up time was 27.1 ± 12.0 months in a cyanoacrylate injection group and 27.6 ± 14.3 months in a BRTO group. Probability of gastric variceal rebleeding was higher in the cyanoacrylate injection group than in the BRTO group (P = 0.024). Probability of remaining free of all-cause rebleeding at 1 and 2 years for cyanoacrylate injection versus BRTO was 77% vs. 96.3% and 65.2% vs. 92.6% (P = 0.004). Survival rates, frequency of complications, and worsening of esophageal varices were similar in both groups. BRTO resulted in fewer hospitalizations, inpatient stays and lower medical costs.
Conclusions: BRTO is more effective than cyanoacrylate injection in preventing rebleeding from GVs, with similar frequencies of complications and mortalities.
