Quality of Life Research

, Volume 28, Issue 1, pp 109–119 | Cite as

Quality-adjusted survival of nivolumab plus ipilimumab or nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma: a quality-adjusted time without symptoms or toxicity (Q-TWiST) analysis

  • David F. McDermottEmail author
  • Ruchit Shah
  • Komal Gupte-Singh
  • Javier Sabater
  • Linlin Luo
  • Marc Botteman
  • Sumati Rao
  • Meredith M. Regan
  • Michael Atkins



To compare the quality-adjusted survival of nivolumab plus ipilimumab combination and nivolumab alone versus ipilimumab alone among treatment-naive patients with advanced melanoma based on a minimum 36-month follow-up from the CheckMate 067 trial.


Overall survival was partitioned into time without symptoms of progression or toxicity (TWiST), time with treatment-related grade ≥ 3 adverse events after randomization but before progression (TOX), and time from progression until end of follow-up or death (REL). Mean quality-adjusted TWiST (Q-TWiST) was calculated by multiplying the mean time spent in each health state by a utility of 1.0 for TWiST and 0.5 for TOX and REL. Sensitivity analyses included varying utilities of TOX and REL; Q-TWiST gains at different follow-up times were calculated using EQ-5D-3L utilities from the trial. Relative Q-TWiST gain of ≥ 10% was considered clinically important.


Compared with ipilimumab-treated patients, those who received nivolumab + ipilimumab combination had significantly longer TWiST and TOX but shorter REL; nivolumab-treated patients had significantly longer TWiST, shorter REL, and shorter but statistically nonsignificant TOX. Mean Q-TWiST was highest for nivolumab + ipilimumab (23.5 months; 95% CI 21.9–25.2), followed by nivolumab (21.8 months; 95% CI 20.2–23.4) and ipilimumab (15.3 months; 95% CI 13.9–16.6). Relative Q-TWiST gains were favorable and clinically important for nivolumab + ipilimumab combination (+ 36.81%) and nivolumab alone (+ 29.18%) versus ipilimumab alone. Relative gains increased with follow-up from 3 to 40 months for all comparisons. These gains remained consistent in magnitude and direction in the different sensitivity analyses.


Nivolumab + ipilimumab combination and nivolumab alone resulted in a statistically significant and clinically important improvement in quality-adjusted survival compared with ipilimumab alone.


Q-TWiST Advanced melanoma Nivolumab Ipilimumab Quality-adjusted survival 


M stage

Metastases stage


Programmed death 1


Programmed death ligand 1


Quality-adjusted time without symptoms or toxicity


Response evaluation criteria in solid tumors


Time from progression until end of follow-up or death


Time without disease progression or symptoms of toxicity


Time with grade ≥ 3 treatment-related adverse events after randomization but before progression




Upper limit of normal



We thank the patients and their families, the clinical study teams, and the investigators who participated in the CheckMate 067 trial. Editorial assistance was provided by Kakoli Parai, PhD, and Cara Hunsberger at StemScientific, an Ashfield Company, funded by Bristol-Myers Squibb.


This study was supported by Bristol-Myers Squibb.

Compliance with ethical standards

Conflict of interest

David F. McDermott served as a consultant or advisor for Bristol-Myers Squibb, Pfizer, Merck, Novartis, Eisai, Exelixis, Array BioPharma, and Genentech; and his institution received research funding from Prometheus Laboratories and Bristol-Myers Squibb. Ruchit Shah, Linlin Luo, and Marc Botteman are employed by Pharmerit International. Marc Botteman also reports stock ownership in Pharmerit International. Pharmerit International has received research funding from Bristol-Myers Squibb to conduct this research. Pharmerit International is a global health economics and outcomes research consulting firm that receives research funding and fees related to consulting and other advisory roles from numerous private organizations from the pharmaceutical, biotech, device, and medical industry. Komal Gupte-Singh and Sumati Rao are employed by Bristol-Myers Squibb and own stock in Bristol-Myers Squibb. Javier Sabater was a Bristol-Myers Squibb employee at the time this work was conducted and owns stock in Bristol-Myers Squibb. Meredith M. Regan served as a consultant or advisor for Merck and Ipsen; received funding for travel, accommodations and expenses from Bristol-Myers Squibb; and her institution received research funding from Veridex, OncoGenex, Pfizer, Ipsen, Novartis, Merck, Ferring, Celgene, AstraZeneca, Pierre Fabre, Bayer, and Bristol-Myers Squibb. Michael Atkins served as a consultant or advisor for Genentech, Pfizer, Novartis, GlaxoSmithKline, C-Cam, X4 Pharma, Amgen, Lilly, Alkermes, Infinity Pharmaceuticals, Genoptix, Bristol-Myers Squibb, Nektar, and Merck.

Ethical approval

All procedures performed in the CheckMate 067 study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the CheckMate 067 study.

Supplementary material

11136_2018_1984_MOESM1_ESM.docx (88 kb)
Supplementary material 1 (DOCX 87 KB)


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Copyright information

© Springer Nature Switzerland AG 2018

Authors and Affiliations

  • David F. McDermott
    • 1
    Email author
  • Ruchit Shah
    • 2
  • Komal Gupte-Singh
    • 3
  • Javier Sabater
    • 3
    • 6
  • Linlin Luo
    • 2
  • Marc Botteman
    • 2
  • Sumati Rao
    • 3
  • Meredith M. Regan
    • 4
  • Michael Atkins
    • 5
  1. 1.Beth Israel Deaconess Medical Center, Dana-Farber/Harvard Cancer Center, Harvard Medical SchoolBostonUSA
  2. 2.Pharmerit InternationalBethesdaUSA
  3. 3.Bristol-Myers SquibbPrincetonUSA
  4. 4.Dana-Farber Cancer InstituteBostonUSA
  5. 5.Lombardi Cancer CenterGeorgetown UniversityWashingtonUSA
  6. 6.ServierSuresnesFrance

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