The oncologist · 2026
Patterns of progression and survival in patients with mismatch repair deficient/ microsatellite instability- high metastatic colorectal cancer treated with immunotherapy.
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LaPelusa Michael, Shah Preksha, Bhamidipati Deepak, Kui Naishu, Bent Alisha, Dasari Arvind, Huey Ryan, Kee Bryan, Kopetz Scott, Le Phat, Ludford Kaysia, Morelli Maria Pia, Morris Van K, Parseghian Christine, Raghav Kanwal, Willis Jason, Wolff Robert, Zhao Dan, Overman Michael J, Higbie Victoria S
Аннотация
BACKGROUND: Immunotherapy has shown to be efficacious in patients with deficient mismatch repair (dMMR)/microsatellite instability-high (MSI-H) colorectal cancer (CRC). Unfortunately, there is still a population of patients who either do not respond or progress after prior response. Understanding the progression dynamics and outcomes based on the nature of disease progression (PD) is critical in this patient population.
METHODS: We performed a retrospective analysis of 166 patients with advanced dMMR/MSI-H CRC who received immunotherapy. PD patterns were classified as intrinsic (progression at first restaging scan) or adaptive (progression after initial stable/responding disease) and as single organ or systemic.
RESULTS: Progression was seen in 64 patients (38.6%) with single organ progression in 31 (48.4%) and systemic progression in 33 (51.5%). Intrinsic progression was seen in 32 patients (50%) and adaptive progression in 32 (50%). Patients with single organ progression had a longer median TTP (mTTP) and median OS (mOS) compared to patients with systemic progression (mTTP: 8.8 vs 4.0 months, P = .005; mOS: 65.9 vs 18.7 months, P = .023). Patients with adaptive PD had a longer mTTP and mOS compared to patients with intrinsic PD (mTTP: 11.6 vs 1.9 months, P = <.01; mOS: 65.9 months vs 17.0 months, P = .001).
CONCLUSION: This analysis identifies significant differences in outcomes of patients with dMMR/MSI-H CRC based on the pattern and extent of progression, underscoring the need for tailored therapeutic strategies depending on the nature of PD-1-based progression.
METHODS: We performed a retrospective analysis of 166 patients with advanced dMMR/MSI-H CRC who received immunotherapy. PD patterns were classified as intrinsic (progression at first restaging scan) or adaptive (progression after initial stable/responding disease) and as single organ or systemic.
RESULTS: Progression was seen in 64 patients (38.6%) with single organ progression in 31 (48.4%) and systemic progression in 33 (51.5%). Intrinsic progression was seen in 32 patients (50%) and adaptive progression in 32 (50%). Patients with single organ progression had a longer median TTP (mTTP) and median OS (mOS) compared to patients with systemic progression (mTTP: 8.8 vs 4.0 months, P = .005; mOS: 65.9 vs 18.7 months, P = .023). Patients with adaptive PD had a longer mTTP and mOS compared to patients with intrinsic PD (mTTP: 11.6 vs 1.9 months, P = <.01; mOS: 65.9 months vs 17.0 months, P = .001).
CONCLUSION: This analysis identifies significant differences in outcomes of patients with dMMR/MSI-H CRC based on the pattern and extent of progression, underscoring the need for tailored therapeutic strategies depending on the nature of PD-1-based progression.