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OA14 - Update of Phase 3 Trials and the Role of HPD (ID 148)
- Event: WCLC 2019
- Type: Oral Session
- Track: Immuno-oncology
- Presentations: 1
- Now Available
OA14.06 - Hyperprogressive Disease in Advanced Non–Small Cell Lung Cancer Patients Treated with Immune Checkpoint Inhibitors (Now Available) (ID 1835)
11:30 - 13:00 | Author(s): Silvia Brich
Hyperprogressive disease (HPD) is a paradoxical boost in tumour growth described in a subset of cancer patients treated with immune checkpoint inhibitors (ICIs).Method
We retrospectively collected data about all consecutive patients with advanced Non-Small Cell Lung Cancer (aNSCLC) treated with ICIs at our Institution between 04/2013 and 12/2018. Patients were classified according to our previously published clinical/radiological criteria for HPD (Lo Russo G, Clin Canc Res 2018). (Table). All ICIs administered for ≥1 cycle were admitted. Chi-square test was used to compare qualitative variables. Survival was estimated with Kaplan-Meier method. Log-rank test was used to compare curves. Multivariate analyses were performed with Cox hazard model.
Table HPD definition on the basis of 3 concomitant out of the five possible criteria
HPD CLINICAL & RADIOLOGICAL CRITERIA
Time-to-treatment failure < 2 months
Increase of ≥ 50% in the sum of target lesions major diameters between baseline and first radiological evaluation
Appearance of at least two new lesions in an organ already involved between baseline and first radiological evaluation
Spread of the disease to a new organ between baseline and first radiological evaluation
Clinical deterioration with decrease in ECOG performance status ≥ 2 during the first 2 months of treatment
We reviewed 301 cases and 257 were evaluable for response. We identified four categories: responders (R, 57 cases, 22.2%), patients with stable disease as best response (SD, 69 cases, 26.8%), patients with progressive disease as best response (P, 78 cases, 30.4%) and patients with HPD (53 cases, 20.6%). Clinical/pathological variables were uniformly distributed among groups, except for a higher rate of patients with Eastern Cooperative Oncology Group Performance Status (ECOG-PS) >1 in HPD group (p = 0.0141). After a median follow-up of 23.49 months (IQR 10.72–44.21 months), median Progression-Free Survival (mPFS) and median Overall Survival (mOS) were 14,2 vs 6,5 vs 2,3 vs 1,5 months ( p < 0.0001) and 32,5 vs 17,8 vs 7,8 vs 4,1months (p < 0.0001) in R, SD, P and HPD group, respectively. The multivariate analyses, between P and HPD groups, adjusted for ICIs line, number of metastatic sites and ECOG-PS according to PFS (HR 2.448, 95% CI 2.137-2.899, p<0.0001) and OS (HR 2.481, 95%CI 2.092-2.950, p < 0.0001) confirmed the worse outcome of HPD group.Conclusion
Our updated analysis confirmed patients with HPD as a distinct category that performs significantly worse than other groups, including P patients. The incidence of HPD in our cohort is relevant. The ICIs’ detrimental effect has to be taken into account and further investigated.
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