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Attend this session at the
2019 ASCO Annual Meeting!


Session: Gastrointestinal (Noncolorectal) Cancer

Type: Poster Session

Time: Monday June 3, 8:00 AM to 11:00 AM

Location: Hall A

Homologous recombination deficiency (HRD): A biomarker for first-line (1L) platinum in advanced pancreatic ductal adenocarcinoma (PDAC).

Sub-category:
Pancreatic Cancer

Category:
Gastrointestinal (Noncolorectal) Cancer

Meeting:
2019 ASCO Annual Meeting

Abstract No:
4132

Poster Board Number:
Poster Session (Board #237)

Citation:
J Clin Oncol 37, 2019 (suppl; abstr 4132)

Author(s): Wungki Park, Winston Wong, Kenneth H. Yu, Anna M. Varghese, Nadeem Riaz, Vinod P. Balachandran, Imane H. El Dika, Nitya Prabhakar Raj, Danny Khalil, Geoffrey Yuyat Ku, Neil Howard Segal, Jia Li, Sree Bhavani Chalasani, Curtis Robert Chong, David Paul Kelsen, Ghassan K. Abou-Alfa, Michael F. Berger, Nikolaus Schultz, Christine A Iacobuzio-Donahue, Eileen Mary O'Reilly; Memorial Sloan Kettering Cancer Center, Department of Medicine, Gastrointestinal Oncology, New York, NY; Memorial Sloan Kettering Cancer Center, New York City, NY; Memorial Sloan Kettering Cancer Center/Weill Cornell Medical College, New York, NY; Memorial Sloan Kettering Cancer Center, New York, NY; Thoracic Oncology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center and Weill Cornell Medical College, New York, NY; Yale School of Medicine, Yale University, New Haven, CT; Memorial Sloan Kettering Cancer Center, Livingston, NJ

Abstract Disclosures

Abstract:

Background: HRD is an emerging biomarker for platinum therapy in PDAC. The clinical implications regarding differences in outcome between germline and somatic HRD in advanced PDAC treated with 1L platinum is unexplored. Methods: We evaluated overall survival (OS) for advanced PDAC (stage III/IV) based on their pathogenic germline (gHRD) and somatic HRD (sHRD) using integrated genomic profiling from MSK-IMPACT and 1L platinum use. HRD defined by pathogenic alterations from the following genes: BRCA1/2, PALB2, ARID1A/B/2, ATR, ATRX, ATM, BAP1, RAD50/51C/D, BRIP1, NBN, CHECK1/2, FANCA/C, CDK12, and MRE11. Results: Advanced PDAC patients (n=461) treated at MSK enrolled in a prospective database, were evaluated. Median follow-up was 27.6 months (95% CI, 24.6-30.6). Both germline and somatic profilings were available for n=350 (76%) but only somatic profiling was available for n=111 (24%). We identified n=52 patients with gHRD (11.3%), n=42 patients with sHRD (9.1%), and 48 patients with somatic VUS for HRD genes. From all 461 patients, the OS was not different between 1L non-platinum vs. 1L platinum groups (19 M vs. 19.3 M), regardleess of their HRD status. (Table) The OS was superior for gHRD vs. non-gHRD (28.7 M vs. 18.2 M), regardless of 1L treatment choice. However, similar significant OS superiority was neither observed in sHRD vs. non-sHRD, nor in VUS sHRD vs. non-VUS sHRD. In a subgroup analysis of 1L platinum treated patients, the OS was superior in gHRD vs. non-gHRD (NR vs. 17.9 M); however, there was no OS difference between sHRD and non-sHRD. Conclusions: In advanced PDAC patients, only gHRD predicted better overall survival for first-line platinum chemotherapy. These findings emphasize the importance of germline mutation testing of HRD in PDAC. Biomarker validation and functional definition of HRD such as loss of heterozygosity analysis is underway.

(N)All treatments (461)
1L non-platinum (184)
1L platinum (277)
OS (M)HRp-valueOS (M)HRp-valueOS (M)HRp-value
All pts (461)19.0--19.0--19.30.950.676
No gHRD (409)18.20.540.00318.80.740.41917.90.470.004
HRD (52)27.724.3NR
No sHRD (419)18.30.920.67018.20.680.25218.31.120.666
sHRD (42)21.523.820.6

Overall survivals for different HRD groups and 1L treatment groups.

 
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1. Olaparib as maintenance treatment following first-line platinum-based chemotherapy (PBC) in patients (pts) with a germline BRCA mutation and metastatic pancreatic cancer (mPC): Phase III POLO trial.

Meeting: 2019 ASCO Annual Meeting Abstract No: LBA4 First Author: Hedy L. Kindler
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2. APACT: phase III, multicenter, international, open-label, randomized trial of adjuvant nab-paclitaxel plus gemcitabine (nab-P/G) vs gemcitabine (G) for surgically resected pancreatic adenocarcinoma.

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3. Randomized phase II study of second-line modified FOLFIRI with PARP inhibitor ABT-888 (Veliparib) (NSC-737664) versus FOLFIRI in metastatic pancreatic cancer (mPC): SWOG S1513.

Meeting: 2019 ASCO Annual Meeting Abstract No: 4014 First Author: E. Gabriela Chiorean
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