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Positive Health-Related Quality of Life outcomes with pembrolizumab monotherapy in unresectable or metastatic MSI-H/dMMR solid tumours

Previously, the Keynote-158 study of pembrolizumab demonstrated a high objective response rate with a durable clinical benefit in unresectable or metastatic microsatellite instability-high/mismatch repair deficient (MSI-H/dMMR) solid tumours. Exploratory health-related quality of life (HRQoL) assessments now indicate that pembrolizumab monotherapy generally improved or preserved HRQoL, with the greatest improvements observed in patients who achieved a complete or partial response.

Pembrolizumab is currently licensed for the treatment of unresectable or metastatic MSI-H/ dMMR) solid tumours that progressed on prior therapy, based on the results from the open-label, multicohort, phase II Keynote-158 study. This study demonstrated a median progression-free survival (PFS) of 3.5 months (95%CI: 2.3-4.2 months), a median overall survival (OS) of 20.1 months (95%CI]: 14.1-27.1) and an overall response rate (ORR) of 30.8%. Additionally, the duration of response (DoR) lasted ≥36 months in 70.1% of responders. At the 2021 ESMO World Congress on Gastrointestinal Cancer, health-related quality of life (HRQoL) outcomes in patients with MSI-H/dMMR tumours (cohort K) in this study were presented. 

Keynote-158 study design

Keynote-158 is open-label, phase II trial that enrolled 351 patients in cohort K. To be eligible for this cohort, patients were required to have advanced MSI-H solid tumours, excluding colorectal cancer, that have progressed or are intolerant to at least one line of therapy. Eligible patients were also required to have an ECOG PS score of 0-1. Tumour samples were also taken for separate biomarker assessment. Patients received pembrolizumab (200 mg intravenously every 3 weeks) for up to 35 cycles, or until unacceptable toxicity, disease progression or patient withdrawal. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30) and the EuroQol group EQ-5D-3L questionnaires were administered from baseline, regular intervals throughout treatment and 30 days after treatment discontinuation. The prespecified analyses included change from baseline in all patients overall, and by best overall response for QLQ-C30 global health status (GHS)/QoL QLQ-C30 functional/symptom scales/items, and EQ-5D-3L visual analogue scale (VAS) score, as well as the proportion of patients who had QLQ-C30 scores that ‘improved’ or ‘worsened’ (defined as ≥10 point change) or ‘remained stable’ from baseline. 


Of the 351 patients enrolled in cohort K, 311 completed a baseline QLQ-C30 and 315 completed a baseline EQ-5D-3L questionnaire. Compliance was high, with both questionnaires having a completion rate of 88% at week nine. The mean change in GHS/QoL score from baseline to week nine for all patients was 3.07 (0.19-5.94), and was sustained or improved over time through week 111. Patients who achieved a complete or partial response (CR/PR) saw the greatest mean change in GHS (10.85 [6.36-15.35]), whilst patients with stable disease reported a mean change of 2.36 [-2.48-7.20]). Unsurprisingly, patients who experienced progressive disease had the worse mean change in GHS (-3.70 [-8.49-1.08]). Improvements were also observed in role functioning (4.26 [0.61‒7.90]). No differences were observed for social (1.88 [−1.67 to 5.42]), emotional (1.19 [−1.28 to 3.66]), physical (−0.06 [−2.54 to 2.42]), and cognitive (−2.09 [−4.44 to 0.25]) functioning. For patients who achieved a CR/PR, improvements in physical (5.58 [1.91‒9.25]), role (9.88 [3.80‒15.97]), emotional (5.62 [1.56‒9.68]), and social (8.33 [2.70‒13.97]) functioning were observed (no difference for cognitive functioning; 1.74 [−1.45 to 4.94]). Symptoms that showed improvements in all patients included pain (−4.69 [−8.46 to −0.92]), insomnia (−4.76 [−8.52 to −1.00]), and appetite loss (−4.47 [−8.15 to −0.79]). Over 70% of patients experienced either improved or stable scores at week nine for GHS/QoL (improved, 32.0%; stable, 45.9%) and all functional and symptom scales/items. Largest improvements were seen for fatigue (40.3%), pain (39.8%), role functioning (35.1%), social functioning (29.9%), insomnia (28.6%), and appetite loss (28.1%). Patients who achieved a CR/PR also experienced the greatest mean change in EQ-5D-3L VAS score (6.74 [3.51-9.96]). In contrast, patients with progressive disease had the worst mean change (-1.88 [-5.62-1.86]). Overall, all patients experienced a marginal increase in mean change (2.88 [0.72-5.03]) and scores remained stable or improved over time through week 111.


Monotherapy with pembrolizumab either improved or preserved HRQoL in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours. Furthermore, the greatest improvements were seen in patients who achieved a CR or PR. When combined with the high ORR and durable clinical benefit, this HRQoL data further support the use of pembrolizumab monotherapy in patients with previously treated MSI-H/dMMR advanced non-colorectal solid tumours.


Maio M, et al, Health-Related Quality of Life in Patients Treated With Pembrolizumab for Microsatellite Instability-High/Mismatch Repair Deficient Advanced Solid Tumors: Results From the KEYNOTE-158 Study. Presented at the 2021 ESMO World Congress on Gastrointestinal Cancer; Abstract SO-8.

Speaker Michele Maio

Michele Maio

Michele Maio, MD, PhD, University Hospital of Siena, Italy


See: Keyslides

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