Pembrolizumab monotherapy demonstrated improvement in health-related quality of life in patients with previously treated metastatic microsatellite instability-high/ mismatch repair deficient advanced noncolorectal solid tumors, with the biggest improvements seen in those who achieved a complete remission or partial remission.
Pembrolizumab (Keytruda) monotherapy demonstrated improvement in health-related quality of life (HRQoL) in patients with previously treated metastatic microsatellite instability-high (MSI-H)/ mismatch repair deficient (dMMR) advanced noncolorectal solid tumors, with the biggest improvements seen in those who achieved a complete remission (CR) or partial remission (PR), according to data from a cohort of the KEYNOTE-158 study presented at the ESMO World Congress on Gastrointestinal Cancer 2021.
The KEYNOTE-158 study (NCT02628067) lead to the approval of pembrolizumab for MSI-HMMR deficient solid tumors that progressed on prior therapy. The agent produced a high overall response rate (ORR) of 30.8% with a greater than 36-month median duration of response (DoR) in 70.1% of those who responded. The median progression-free survival (PFS) was 3.5 months (95% CI, 2.3-4.2), and the median overall survival (OS) was 20.1 months (95% CI, 14/1-27.1).
Cohort K included 351 patients with any advanced solid tumor that is MSI-H, excluding those with colorectal cancer, who had progressed or were intolerable to 1 or more prior lines of therapy, have measurable disease per RECIST v1.1, an ECOG performance status of 0 or 1, and a provision of tumor samples available for biomarker assessment. Patients in this cohort received 200 mg of pembrolizumab for up to 35 cycles. Treatment continued until diseae progression, unacceptable toxicity, investigator decision, or withdrawal of consent.
The exploratory end point for this cohort was change from baseline to week 9 in HRQo, and the proportion of patients who had QLQ-C30 scores that either improved or worsened by 10 points or remained stable from baseline. Data on HRQoL was self-reported by patients using 2 questionnaires that was administered at baseline, at regular intervals throughout treatment, and 30 days after treatment discontinuation. The first questionnaire was the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C20) and the EuroQol group EQ-5D-3L questionnaire.
At a October 5, 2020 data cutoff, 311 patients completed the QLQ-C30 questionnaire, and 315 patients completed the EG-5D-3L questionnaire. The compliance rate at baseline was 93% and 94% respectively, and 88% for both questionnaires at week 9.
The greatest improvements from baseline were seen in patients with PR or CR. The results also shows that QLQ-C30 GHS/QoL scores improved from baseline at week 9 and remained stable over time through week 111. The mean from baseline to week 9 for all patients was 3.07 points (95% CI, 0.19-5.94). For patients with CR/PR, it was 10.85 points (95% CI, 6.36-15.35). For patients with stable disease (SD), the change from baseline was 2.36 points (95% CI, -2.48 to 1.08), and for patients with progressive disease (PD), -3.70 (95% CI, -8.49 to 1.08).
Overall, means in improvements were seen in role functioning with a mean of 4.26 points (95% CI, 0.61‒7.90). However, no differences were observed for social with a mean of 1.88 points (95% CI, -1.67 to 5.42), emotional with a mean of 1.19 (-1.28 to 3.66), physical with a mean of -0.06 points (95% CI, -2.54 to 2.42), and cognitive with a mean of -2.09 points (95% CI, -4.44 to 0.25) functioning. Patients who achieved a CR or PR saw improvements in physical with a mean of 5.58 (95% CI, 1.91‒9.25), role with a mean of 9.88 points (95% CI, 3.80‒ 15.97), emotional with a mean of 5.62 points (95% CI, 1.56‒9.68), and social with a mean of 8.33 points (95% CI, 2.70‒13.97) functioning. No differences were seen in cognitive functioning with a mean of 1.74 points (95% CI, -1.45 to 4.94).
Improvements in several symptoms such as pain, which improved by a mean of -4.69 points (95% CI, -8.46 to -0.92), insomnia by a mean of -4.76 points (95% CI, -8.52 to -1.00), and appetite loss with a mean of -4.47 points (95% CI, -8.15 to -0.79) were observed in all patients, not just those who experienced CR or PR. At week 9, over 70% of patients had a stable (45.9%) or improved (32.0%) score with all functional items or symptom scales. In total, a 40.3% improvement was seen for fatigue, a 39.8% improvement was seen for pain, a 35.1% improvement was seen for role functioning, a 29.9% improvement was seen for social functioning, a 28.6% improvement was seen for insomnia, and a 28.1% improvement was seen for appetite loss.
“Together with high ORR and durable clinical benefit, these findings further support the benefit of pembrolizumab monotherapy in patients with previously treated MSI-H/dMMR advanced noncolorectal solid tumors,” wrote study author Michele Maio, MD, PhD, the director of the Division of Medical Oncology and Immunotherapy at the University Hospital of Siena.2