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Poster display session

1476 - Checkpoint inhibitors in MSI tumors: Lessons from a monocentric experience

Date

10 Sep 2017

Session

Poster display session

Presenters

Yolla El Dakdouki

Citation

Annals of Oncology (2017) 28 (suppl_5): v403-v427. 10.1093/annonc/mdx376

Authors

Y. El Dakdouki1, L. Verlingue1, C. Massard2, A. Leary3, L. Lacroix4, E. Rouleau5, J. Scoazec6, O. Caron7, P. Benusiglio7, P. Kannouche8, A. Hollebecque9, D. Malka10, J. Soria11, A. Marabelle12

Author affiliations

  • 1 Duertec, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 2 Medical Oncology, Institut de cancérologie Gustave Roussy, Villejuif/FR
  • 3 Gynecology Unit, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 4 Bmo, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 5 Département De Biologie Et Pathologie Médicales, Gustave ROUSSY, 94805 - VILLEJUIF/FR
  • 6 Pathology, Gustave Roussy Institute, Villejuif/FR
  • 7 Genetics, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 8 Immunology, Gustave Roussy Institute, Villejuif/FR
  • 9 Drug Development Department (ditep), Gustave Roussy Cancer Campus, 94805 - Villejuif/FR
  • 10 Department Of Cancer Medicine, Institut de cancérologie Gustave Roussy, 94800 - Villejuif/FR
  • 11 Medical Oncology, Institut Gustave Roussy, 94800 - Villejuif/FR
  • 12 Département D’innovation Thérapeutique Et D’essais Précoces, Gustave Roussy, Université Paris-Saclay, Villejuif/FR
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Resources

Abstract 1476

Background

Microsatellite unstable (MSI) tumors have showed high response rates to checkpoint inhibitors. Nonetheless, patterns of response and characteristics of responders remain poorly understood. We hereby report preliminary results of response to immunotherapy in a cohort of patients (pts) with metastatic MSI tumors.

Methods

We included all pts with metastatic MSI tumors of various histologic types treated at our institute with checkpoint inhibitors as monotherapy or combinations. Somatic MSI status has been identified by immunohistochemistry with PCR at diagnosis and/or whole-exome sequencing in molecular screening trials at metastatic stage. Pts not previously known to have Lynch syndrome (LS) have been tested for inherited germline defect.

Results

From November 2014 through April 2017, 43 pts were enrolled. Main pts characteristics were as follow [median (range)]: age at treatment was 56.4 years (26-78) and number of previous treatment lines was 2 (1-5). The most frequently treated histologic types were gastro-intestinal (22/43: 15 colorectal (CRC), 2 small bowel, 2 biliary, 2 pancreatic, 1 duodenal) and gynecologic (11/43: 8 endometrial, 3 ovarian) tumors. Diagnosis of hereditary LS has been confirmed in 12 pts (28%) and screening results are awaited in 6 pts. After a median follow-up of 5.6 months and treatment with a median of 7 cycles (Range 1-47), median overall survival was not reached (NR) and median progression-free survival (PFS) was 11.1 months (95% CI 2.8-19.5). In the 38 evaluable pts who received more than 2 cycles, overall objective response (ORR) and stable disease rates were 31.6% (12/38; 4 complete responses (CR), 8 partial responses (PR)) and 18.4% (7/38) respectively. ORR was 33.3% (5/15; 4 CR, 1 PR) in CRC and 30.4% (7 PR/23) in non-CRC. PFS was significantly better in confirmed LS than sporadic tumors (NR and 5 months, respectively, p = 0.028) and in CRC than non-CRC (NR and 5.6 months, respectively, p = 0.025) in univariate analysis.

Conclusions

We reported high response rates and survival benefit with checkpoint inhibitors in pts with MSI tumors remarkably in CRC and LS. A comprehensive analysis of immune microenvironment would be of clinical interest to characterize responders and non-responders.

Clinical trial identification

Legal entity responsible for the study

Gustave Roussy Cancer Campus

Funding

Gustave Roussy Cancer Campus

Disclosure

All authors have declared no conflicts of interest.

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