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NSCLC, metastatic

4840 - Hyperprogressive disease (HPD) is frequent in non-small cell lung cancer (NSCLC) patients (pts) treated with anti PD1/PD-L1 monoclonal antibodies (IO).

Date

10 Sep 2017

Session

NSCLC, metastatic

Presenters

Roberto Ferrara

Citation

Annals of Oncology (2017) 28 (suppl_5): v460-v496. 10.1093/annonc/mdx380

Authors

R. Ferrara1, C. CARAMELLA2, M. Texier3, C. Audigier Valette4, L. Tessonnier5, L. Mezquita1, J. Lahmar1, J. Mazieres6, G. Zalcman7, S. Brosseau7, V. Westeel8, S. Le Moulec9, L. Leroy9, B. Duchemann10, R. Veillon11, D. Planchard1, M. Boucher1, S. Koscielny3, J. Soria12, B. Besse1

Author affiliations

  • 1 Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2 Radiology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 3 Biostatistiques Et Epidémiologie, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4 Pneumology Department, Centre Hospitalier Toulon Sainte-Musse, 83100 - Toulon/FR
  • 5 Nuclear Medicine, Centre Hospitalier Toulon Sainte-Musse, Toulon/FR
  • 6 Thoracic Oncology Department, Toulouse University Hospital, Toulouse/FR
  • 7 Thoracic Oncology, Hôpital Bichat-Claude Bernard, Université Paris-Diderot, 75018 - Paris/FR
  • 8 Pneumology Department, CHU Besançon, Hôpital Jean Minjoz, 25030 - Besançon/FR
  • 9 Medical Oncology, Institute Bergonié, 33076 - Bordeaux/FR
  • 10 Medical Oncology, Hôpital Avicenne, 93009 - Bobigny/FR
  • 11 Medical Oncology, CHU de Bordeaux-Hôpital Haut-Lévêque, 33604 - Pessac/FR
  • 12 Department Of Drug Development, Gustave Roussy Cancer Campus and University Paris-Sud, 94800 - Villejuif/FR
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Abstract 4840

Background

Using Tumor Growth Rate (TGR), we previously described HPD in 10% of 89 NSCLC pts treated with IO in a single institution. In this retrospective study, we explored HPD in a larger and multicenter cohort of advanced NSCLC pts treated with IO.

Methods

We performed a clinical and radiological retrospective analysis of consecutive NSCLC pts, treated with IO, in 5 different institutions, between November 2012 and March 2017. Eligibility criteria required, for each patient, 3 CT scans performed before IO, at baseline and during IO respectively, centrally reviewed by a senior radiologist and assessed according to RECIST 1.1 criteria. We calculated TGR at baseline of IO (baseline CT scan (n) vs (n-1) CT scan), TGR during IO (n + 1 CT scan vs baseline) and the variation per month of TGR between both (delta TGR). Pts were defined HPD if the absolute delta TGR increased by at least 50%. Median overall survival (mOS) and median progression free survival (mPFS) were estimated using the Kaplan-Meier method and compared between HPD and not HPD using the log-rank test.

Results

242 pts were eligible. 64% were male, 50% ≥65 years, 51% smokers, 10% PS ≥ 2, 63% adenocarcinoma. 19% of NSCLC had KRAS mutation, 2% EGFR mutation, 2% ALK rearrangement, 35% had unknown molecular status. PD-L1 expression was positive in 12% of pts, negative in 11% and unknown in 77%, more than 90% of pts received single agent PD1-inhibitor in ≥ 2 line. Response rate (RR) to IO, mPFS and mOS were respectively 15%, 3.9 months (m) [3; 5], 13.4m [9; 42], median follow up was 10m [8; 12]. Compared to baseline, TGR decreased during IO (delta TGR ≤0) in 64% of pts, increased (delta TGR>0) in 36% (not regressing tumors). 40 pts (16%) had HPD. Only 3 pts (1,2%) had confirmed pseudoprogression, 2 of them were initially qualified as HPD. Tumor burden baseline, clinical, molecular, pathological characteristics, PD-L1 status and RR to treatment before IO were not different between HPD and not-HPD pts. Compared to not-HPD population, HPD pts had significantly lower mPFS (1.4 vs 4.9m, p 

Conclusions

HPD occurs in 16% of 242 advanced NSCLC pts treated with IO, leading to decreased survival. Further work is needed to better characterize this population.

Clinical trial identification

Legal entity responsible for the study

Benjamin Besse

Funding

Gustave Roussy

Disclosure

C. Audigier Valette: Bristol Myers Squibb V. Westeel: BMS, MSD, Merck, AZ B. Duchemann: Bristol-Myers Squibb, Roche D. Planchard: AstraZeneca Boehringer Ingelheim BMS Lilly MSD Pfizer Roche Novartis Chugai J-C. Soria: AstraZeneca, Astex, Clovis, GSK, Gammamabs, Lilly, MSD, Mission Therapeutics, Merus, Pfizer, Pharmamar Pierre Fabre, Roche-Genentech, Sanofi, Servier, Symphogen, Takeda. All other authors have declared no conflicts of interest.

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