Indirect Treatment Comparison of Talimogene Laherparepvec Compared with Ipilimumab and Vemurafenib for the Treatment of Patients with Metastatic Melanoma

TY - JOUR

T1 - Indirect Treatment Comparison of Talimogene Laherparepvec Compared with Ipilimumab and Vemurafenib for the Treatment of Patients with Metastatic Melanoma

AU - Quinn, Casey

AU - Ma, Qiufei

AU - Kudlac, Amber

AU - Palmer, Stephen

AU - Barber, Beth

AU - Zhao, Zhongyun

N1 - Publisher Copyright: © 2016, The Author(s).

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Introduction: Few randomized controlled trials have compared new treatments for metastatic melanoma. We sought to examine the relative treatment effect of talimogene laherparepvec compared with ipilimumab and vemurafenib. Methods: A systematic literature review of treatments for metastatic melanoma was undertaken but a valid network of evidence could not be established because of a lack of comparative data or studies with sufficient common comparators. A conventional adjusted indirect treatment comparison via network meta-analysis was, therefore, not feasible. Instead, a meta-analysis of absolute efficacy was undertaken, adjusting overall survival (OS) data for differences in prognostic factors between studies using a published algorithm. Results: Four trials were included in the final indirect treatment comparison: two of ipilimumab, one of vemurafenib, and one of talimogene laherparepvec. Median OS for ipilimumab and vemurafenib increased significantly when adjustment was applied, demonstrating that variation in disease and patient characteristics was biasing OS estimates; adjusting for this made the survival data more comparable. For both ipilimumab and vemurafenib, the adjustments improved Kaplan–Meier OS curves; the observed talimogene laherparepvec OS curve remained above the adjusted OS curves for ipilimumab and vemurafenib, showing that long-term survival could differ from the observed medians. Conclusion: Even with limited data, talimogene laherparepvec, ipilimumab, and vemurafenib could be compared following adjustments, thereby providing a more reliable understanding of the relative effect of treatment on survival in a more comparable patient population. The results of this analysis suggest that OS with talimogene laherparepvec is at least as good as with ipilimumab and vemurafenib and improvement was more pronounced in patients with no bone, brain, lung or other visceral metastases. Funding: Amgen Inc.

AB - Introduction: Few randomized controlled trials have compared new treatments for metastatic melanoma. We sought to examine the relative treatment effect of talimogene laherparepvec compared with ipilimumab and vemurafenib. Methods: A systematic literature review of treatments for metastatic melanoma was undertaken but a valid network of evidence could not be established because of a lack of comparative data or studies with sufficient common comparators. A conventional adjusted indirect treatment comparison via network meta-analysis was, therefore, not feasible. Instead, a meta-analysis of absolute efficacy was undertaken, adjusting overall survival (OS) data for differences in prognostic factors between studies using a published algorithm. Results: Four trials were included in the final indirect treatment comparison: two of ipilimumab, one of vemurafenib, and one of talimogene laherparepvec. Median OS for ipilimumab and vemurafenib increased significantly when adjustment was applied, demonstrating that variation in disease and patient characteristics was biasing OS estimates; adjusting for this made the survival data more comparable. For both ipilimumab and vemurafenib, the adjustments improved Kaplan–Meier OS curves; the observed talimogene laherparepvec OS curve remained above the adjusted OS curves for ipilimumab and vemurafenib, showing that long-term survival could differ from the observed medians. Conclusion: Even with limited data, talimogene laherparepvec, ipilimumab, and vemurafenib could be compared following adjustments, thereby providing a more reliable understanding of the relative effect of treatment on survival in a more comparable patient population. The results of this analysis suggest that OS with talimogene laherparepvec is at least as good as with ipilimumab and vemurafenib and improvement was more pronounced in patients with no bone, brain, lung or other visceral metastases. Funding: Amgen Inc.

KW - Efficacy

KW - Ipilimumab

KW - Meta-analysis

KW - Metastatic melanoma

KW - Oncology

KW - Oncolytic immunotherapy

KW - Talimogene laherparepvec

KW - Vemurafenib

UR - http://www.scopus.com/inward/record.url?scp=84961171033&partnerID=8YFLogxK

U2 - 10.1007/s12325-016-0313-x

DO - 10.1007/s12325-016-0313-x

M3 - Article

C2 - 26979173

AN - SCOPUS:84961171033

SN - 0741-238X

VL - 33

SP - 643

EP - 657

JO - Advances in therapy

JF - Advances in therapy

IS - 4

ER -