Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial

Thewis, André; Amonkar, Mayur M.; Norquist, Josephine M.; Shiu, Kai Keen; Kim, Tae Won; Jensen, Benny Vittrup; Jensen, Lars Henrik; Punt, Cornelis J.A.; Smith, Denis; Garcia-Carbonero, Rocío; Sevilla, Isabel; Fouchardière, Christelle de la; Rivera, F.; Élez, Elena; Díaz, Luis A.; Yoshino, Takayuki; Cutsem, Éric Van; Yang, Ping; Farooqui, Mohammed Z.H.; Le, Dung T.

doi:10.1016/s1470-2045(21)00064-4

Cited by 142 publications

(112 citation statements)

References 31 publications

Supporting

Mentioning

105

Contrasting

Unclassified

Order By: Relevance

“…Recently, ICIs have made remarkable achievements in the treatment of gastrointestinal cancer including colorectal cancer, gastric cancer, esophageal cancer, etc. [34][35][36] Several studies have suggested the potential association of PPI use with the risk of gastrointestinal tumor via the regulation of the composition and diversity of gut microbiota. 37,38 In the present study, no included study has focused on gastrointestinal tumor.…”

Section: Discussionmentioning

confidence: 99%

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

et al. 2021

View full text Add to dashboard Cite

Background: The present study aimed to evaluate the effects of concomitant proton pump inhibitor (PPI) use on immune checkpoint inhibitor (ICI) efficacy among advanced cancer patients. Methods and Materials: A systematic literature search of electronic database was performed to identify all potential reports. Then, meta-analyses were conducted to obtain pooled HRs with 95% CIs, which reveal the influence of PPI use on PFS and OS in patients receiving ICI treatment. Results: A total of 7 studies with 3,647 advanced cancer patients fulfilled the inclusion criteria. The impact of PPI use was then evaluated on 3,340 patients for PFS and 3,647 patients for OS. Concomitant PPI use has a detrimental effect on the efficacy of ICIs that PPI use increased the risk of progression by 28% (HR = 1.28, 95% CI 1.17-1.40; I2 = 31.3%, Q test P = .21) when compared to those not receiving PPIs. Similarly, the meta-analysis showed that PPI use was also associated with shorter OS of advanced cancer patients receiving ICIs that PPI use increased risk of death by 39% (HR = 1.39, 95% CI 1.26-1.54; I2 = 36.5%, Q test P = .16). Sensitivity analysis showed that the pooled HRs were constant after excluding one study at a time, and no significant publication biases were detected. Conclusion:The meta-analysis suggested that concomitant PPI use is significantly associated with low clinical benefit in ICI treatment, revealing a significantly reduced PFS and OS in advanced cancer patients receiving ICIs who are also exposed to PPI.

show abstract

Section: Discussionmentioning

confidence: 99%

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

et al. 2021

View full text Add to dashboard Cite

show abstract

“…QALYs in the model were calculated by adjusting survival time by health-related quality of life. We assigned a utility of 0.84 for patients receiving pembrolizumab in the first setting and 0.77 for those receiving chemotherapy in the first setting, respectively, based on quality-of-life data collected in the KEYNOTE-177 trial ( Andre et al, 2021 ). A utility value of 0.65 and 0.35 from previously published economic evaluation was assigned for patients receiving subsequent active treatments and best supportive care, respectively ( Goldstein et al, 2015 ; Chu et al, 2019 ).…”

Section: Methodsmentioning

confidence: 99%

Cost-Effectiveness of First-Line Versus Second-Line Pembrolizumab or Chemotherapy in Patients With Microsatellite-Instability-High/Mismatch Repair-Deficient Advanced Colorectal Cancer

Tan

Zeng

et al. 2021

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Pembrolizumab is a guideline-recommended, both first- and second-line treatment option for microsatellite-instability-high (MSI-H)/mismatch repair-deficient (dMMR)advanced colorectal cancer patients. The aim of the present study is to investigates the health and economic outcomes of three treatment strategies with or without pembrolizumab in MSI-H/dMMR advanced colorectal cancer to define the best treatment strategy from the perspective of the US payer.Methods: A microsimulation model was developed to estimate the cost and effectiveness of three treatment strategies: 1) pembrolizumab used as first-line, 2) pembrolizumab used as second-line and, 3) chemotherapy. Life years (LYs), quality-adjusted LYs (QALYs) and lifetime costs were estimated.Results: The model projected that patients receiving pembrolizumab in the first-line setting gained 5.579 QALYs; this value was 1.501 and 3.941 QALYs more than that for patients receiving pembrolizumab in the second-line setting and chemotherapy, respectively. First-line pembrolizumab strategy dominated second-line pembrolizumab strategy. Compared with chemotherapy, first-line pembrolizumab strategy yielded an incremental cost of $50613.7, which resulted in an ICER of $13441 per QALY.Conclusion: For patients with MSI-H/dMMR advanced colorectal cancer, reserving pembrolizumab for second-line line use is dominated by its first-line use, and first-line use of pembrolizumab is cost-effective compared with chemotherapy.

show abstract

“…Importantly, only 22% of patients experienced grade 3 or 4 side effects in the pembrolizumab, compared with 66% in the chemotherapy group. Improved quality of life was also reported in the pembrolizumab monotherapy group in a follow-up report [ 59 ].…”

Section: Mmr Deficient—msi-high Metastatic Colorectal Cancermentioning

confidence: 69%

Targeting Metastatic Colorectal Cancer with Immune Oncological Therapies

Galbraith

Wood

Steele

2021

Cancers

View full text Add to dashboard Cite

Metastatic colorectal cancer carries poor prognosis, and current therapeutic regimes convey limited improvements in survival and high rates of detrimental side effects in patients that may not stand to benefit. Immunotherapy has revolutionised cancer treatment by restoring antitumoural mechanisms. However, the efficacy in metastatic colorectal cancer, is limited. A literature search was performed using Pubmed (Medline), Web of Knowledge, and Embase. Search terms included combinations of immunotherapy and metastatic colorectal cancer, primarily focusing on clinical trials in humans. Analysis of these studies included status of MMR/MSS, presence of combination strategies, and disease control rate and median overall survival. Evidence shows that immune checkpoint inhibitors, such as anti-PD1 and anti-PD-L1, show efficacy in less than 10% of patients with microsatellite stable, MMR proficient colorectal cancer. In the small subset of patients with microsatellite unstable, MMR deficient cancers, response rates were 40–50%. Combination strategies with immunotherapy are under investigation but have not yet restored antitumoural mechanisms to permit durable disease regression. Immunotherapy provides the potential to offer additional strategies to established chemotherapeutic regimes in metastatic colorectal cancer. Further research needs to establish which adjuncts to immune checkpoint inhibition can unpick resistance, and better predict which patients are likely to respond to individualised therapies to not just improve response rates but to temper unwarranted side effects.

show abstract

Health-related quality of life in patients with microsatellite instability-high or mismatch repair deficient metastatic colorectal cancer treated with first-line pembrolizumab versus chemotherapy (KEYNOTE-177): an open-label, randomised, phase 3 trial

Cited by 142 publications

References 31 publications

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

Effects of concomitant proton pump inhibitor use on immune checkpoint inhibitor efficacy among patients with advanced cancer

Cost-Effectiveness of First-Line Versus Second-Line Pembrolizumab or Chemotherapy in Patients With Microsatellite-Instability-High/Mismatch Repair-Deficient Advanced Colorectal Cancer

Targeting Metastatic Colorectal Cancer with Immune Oncological Therapies

Contact Info

Product

Resources

About