Lesion-level heterogeneity of radiologic progression in patients treated with pembrolizumab
Menée à partir de l'analyse de 9 239 lésions provenant de 1 194 patients ayant reçu un traitement par pembrolizumab pour un mélanome de stade avancé, un cancer du poumon non à petites cellules, un cancer de l'estomac ou un cancer de la jonction oesogastrique, cette étude analyse les différences au niveau de la progression des lésions cancéreuses primitives et des lésions métastatiques constatées aux examens radiologiques
Background : Disease progression is often considered a binary state reflecting presence or absence of response. However, meaningful heterogeneity between metastatic sites of a given patient may exist and may impact therapeutic outcomes. To characterize the heterogeneity of progression with immunotherapy, we evaluated lesion-level dynamics of pembrolizumab-treated patients across three tumor types.
Patients and methods : Individual metastatic lesion dynamics were analyzed retrospectively in patients with advanced melanoma, non–small cell lung cancer (NSCLC), and gastric or gastroesophageal junction (G/GEJ) cancer who received pembrolizumab in KEYNOTE-001 or KEYNOTE-059. Primary progression was defined as radiologic progression per RECIST v1.1 occurring at the first on-treatment study scan (
∼
9-12 weeks, + 2-week window) and secondary progression as progression occurring beyond the first scan (
∼
14 weeks and beyond). The change in sum of target lesions and of individual lesions was examined, as were patterns and timing of progression.
Results : 9 239 individual lesions from 1 194 patients were analyzed. Among patients with primary progression (39% [200/511] of patients with melanoma, 41% [179/432] with NSCLC, 61% [154/251] with G/GEJ cancer), most patients (51-63%) had a mixture of growing, stable, and shrinking lesions. Despite overall primary progression, a minority of patients (19-25%) had tumor growth at every metastatic site and 17-32% had ≥1 shrinking lesion. Among patients with secondary progression (22% [113/511] of patients with melanoma, 27% [117/432] with NSCLC, 18% [44/251] with G/GEJ cancer), few patients had rebound growth (>20% increase in diameter from nadir) in all lesions whereas the majority (74-84%) had sustained regression in ≥1 lesion.
Conclusions : Lesion-level heterogeneity at the time of disease progression was common in pembrolizumab-treated patients, with many patients demonstrating ongoing disease control in a subset of tumor sites. These results may inform clinical decision-making, trial design, and tumor sampling in the future.
Annals of Oncology , article en libre accès, 2021