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Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

ABSTRACT: Background:Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence. Patients and methods:Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5?mg/kg i.v. 3 weekly for 1?year) or standard observation. The primary end point was detection of an 8% difference in 5-year overall survival (OS) rate; secondary end points included disease-free interval (DFI) and distant metastasis-free interval (DMFI). Tumour and blood were analysed for prognostic and predictive markers. Results:Patients (n=1343) recruited between 2007 and 2012 were predominantly stage III (73%), with median age 56?years (range 18-88?years). With 6.4-year median follow-up, 515 (38%) patients had died [254 (38%) bevacizumab; 261 (39%) observation]; 707 (53%) patients had disease recurrence [336 (50%) bevacizumab, 371 (55%) observation]. OS at 5?years was 64% for both groups [hazard ratio (HR) 0.98; 95% confidence interval (CI) 0.82-1.16, P?=?0.78). At 5?years, 51% were disease free on bevacizumab versus 45% on observation (HR 0.85; 95% CI 0.74-0.99, P?=?0.03), 58% were distant metastasis free on bevacizumab versus 54% on observation (HR 0.91; 95% CI 0.78-1.07, P?=?0.25). Forty four percent of 682 melanomas assessed had a BRAFV600 mutation. In the observation arm, BRAF mutant patients had a trend towards poorer OS compared with BRAF wild-type patients (P?=?0.06). BRAF mutation positivity trended towards better OS with bevacizumab (P?=?0.21). Conclusions:Adjuvant bevacizumab after resection of high-risk melanoma improves DFI, but not OS. BRAF mutation status may predict for poorer OS untreated and potential benefit from bevacizumab. Clinical Trial Information:ISRCTN 81261306; EudraCT Number: 2006-005505-64.

SUBMITTER: Corrie PG

PROVIDER: S-EPMC6096737 | biostudies-literature | 2018 Aug

REPOSITORIES: biostudies-literature

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Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Corrie P G PG Marshall A A Nathan P D PD Lorigan P P Gore M M Tahir S S Faust G G Kelly C G CG Marples M M Danson S J SJ Marshall E E Houston S J SJ Board R E RE Waterston A M AM Nobes J P JP Harries M M Kumar S S Goodman A A Dalgleish A A Martin-Clavijo A A Westwell S S Casasola R R Chao D D Maraveyas A A Patel P M PM Ottensmeier C H CH Farrugia D D Humphreys A A Eccles B B Young G G Barker E O EO Harman C C Weiss M M Myers K A KA Chhabra A A Rodwell S H SH Dunn J A JA Middleton M R MR Nathan Paul P Lorigan Paul P Dziewulski Peter P Holikova Sonja S Panwar Udaiveer U Tahir Saad S Faust Guy G Thomas Anne A Corrie Pippa P Sirohi Bhawna B Kelly Charles C Middleton Mark M Marples Maria M Danson Sarah S Lester James J Marshall Ernest E Ajaz Mazhar M Houston Stephen S Board Ruth R Eaton David D Waterston Ashita A Nobes Jenny J Loo Suat S Gray Gill G Stubbings Helen H Gore Martin M Harries Mark M Kumar Satish S Goodman Andrew A Dalgleish Angus A Martin-Clavijo Agustin A Marsden Jerry J Westwell Sarah S Casasola Richard R Chao David D Maraveyas Anthony A Marshall Ernest E Patel Poulam P Ottensmeier Christian C Farrugia David D Humphreys Alison A Eccles Bryony B Dega Renata R Herbert Chris C Price Christopher C Brunt Murray M Scott-Brown Martin M Hamilton Joanna J Hayward Richard Larry RL Smyth John J Woodings Pamela P Nayak Neena N Burrows Lorna L Wolstenholme Virginia V Wagstaff John J Nicolson Marianne M Wilson Andrew A Barlow Clare C Scrase Christopher C Podd Timothy T Gonzalez Michael M Stewart John J Highley Martin M Wolstenholme Virginia V Grumett Simon S Goodman Andrew A Talbot Toby T Nathan Kannon K Coltart Robert R Gee Bruce B Gore Martin M Farrugia David D Martin-Clavijo Agustin A Marsden Jerry J Price Christopher C Farrugia David D Nathan Kannon K Coltart Robert R Nathan Kannon K Coltart Robert R

Annals of oncology : official journal of the European Society for Medical Oncology 20180801 8

<h4>Background</h4>Bevacizumab is a recombinant humanised monoclonal antibody to vascular endothelial growth factor shown to improve survival in advanced solid cancers. We evaluated the role of adjuvant bevacizumab in melanoma patients at high risk of recurrence.<h4>Patients and methods</h4>Patients with resected AJCC stage IIB, IIC and III cutaneous melanoma were randomised to receive either adjuvant bevacizumab (7.5 mg/kg i.v. 3 weekly for 1 year) or standard observation. The primary end point ...[more]

PMID: 30010756

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Project description:PurposeWe conducted the phase III double-blind European Organisation for Research and Treatment of Cancer (EORTC) 1325/KEYNOTE-054 trial to evaluate pembrolizumab versus placebo in patients with resected high-risk stage III melanoma. On the basis of 351 recurrence-free survival (RFS) events at a 1.25-year median follow-up, pembrolizumab prolonged RFS (hazard ratio [HR], 0.57; P < .0001) compared with placebo. This led to the approval of pembrolizumab adjuvant treatment by the European Medicines Agency and US Food and Drug Administration. Here, we report an updated RFS analysis at the 3.05-year median follow-up.Patients and methodsA total of 1,019 patients with complete lymph node dissection of American Joint Committee on Cancer Staging Manual (seventh edition; AJCC-7), stage IIIA (at least one lymph node metastasis > 1 mm), IIIB, or IIIC (without in-transit metastasis) cutaneous melanoma were randomly assigned to receive pembrolizumab at a flat dose of 200 mg (n = 514) or placebo (n = 505) every 3 weeks for 1 year or until disease recurrence or unacceptable toxicity. The two coprimary end points were RFS in the overall population and in those with programmed death-ligand 1 (PD-L1)-positive tumors.ResultsPembrolizumab (190 RFS events) compared with placebo (283 RFS events) resulted in prolonged RFS in the overall population (3-year RFS rate, 63.7% v 44.1% for pembrolizumab v placebo, respectively; HR, 0.56; 95% CI, 0.47 to 0.68) and in the PD-L1-positive tumor subgroup (HR, 0.57; 99% CI, 0.43 to 0.74). The impact of pembrolizumab on RFS was similar in subgroups, in particular according to AJCC-7 and AJCC-8 staging, and BRAF mutation status (HR, 0.51 [99% CI, 0.36 to 0.73] v 0.66 [99% CI, 0.46 to 0.95] for V600E/K v wild type).ConclusionIn resected high-risk stage III melanoma, pembrolizumab adjuvant therapy provided a sustained and clinically meaningful improvement in RFS at 3-year median follow-up. This improvement was consistent across subgroups.

Project description:BackgroundTo identify whether adjuvant transarterial chemoembolization (TACE) can improve prognosis in HCC patients with a low risk of recurrence (tumor size ≤ 5 cm, single nodule, no satellites, and no microvascular or macrovascular invasions) after hepatectomy.MethodsThe data of 489 HCC patients with a low risk of recurrence after hepatectomy from Shanghai Cancer Center (SHCC) and Eastern Hepatobiliary Surgery Hospital (EHBH) were retrospectively reviewed. Recurrence-free survival (RFS) and overall survival (OS) were analyzed with Kaplan-Meier curves and Cox proportional hazards regression models. The effects of selection bias and confounding factors were balanced using propensity score matching (PSM).ResultsIn the SHCC cohort, 40 patients (19.9%, 40/201) received adjuvant TACE, and in the EHBH cohort, 113 patients (46.2%, 133/288) received adjuvant TACE. Compared to the patients without adjuvant TACE after hepatectomy, patients receiving adjuvant TACE had significantly shorter RFS (P=0.022; P=0.014) in both cohorts before PSM. However, no significant difference existed in OS (P=0.568; P=0.082). Multivariate analysis revealed that serum alkaline phosphatase and adjuvant TACE were independent prognostic factors for recurrence in both cohorts. Furthermore, significant differences existed in tumor size between the adjuvant TACE and non-adjuvant TACE groups in the SHCC cohort. There were differences in transfusion, Barcelona Clinic Liver Cancer stage and tumor-node-metastasis stage in the EHBH cohort. These factors were balanced by PSM. After PSM, patients with adjuvant TACE after hepatectomy still had significantly shorter RFS than those without (P=0.035; P=0.035) in both cohorts, but there was no difference in OS (P=0.638; P=0.159). Adjuvant TACE was the only independent prognostic factor for recurrence in multivariate analysis, with hazard ratios of 1.95 and 1.57.ConclusionsAdjuvant TACE may not improve long-term survival and might promote postoperative recurrence in HCC patients with a low risk of recurrence after hepatectomy.

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Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

Publications

Adjuvant bevacizumab for melanoma patients at high risk of recurrence: survival analysis of the AVAST-M trial.

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