Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer
Abstract
:1. Introduction
2. Patients and Methods
2.1. Cancer Gene Panel Profiling
2.2. Clinical Trial
2.3. Diagnostic Testing for H. pylori Infection
2.4. Ethical Considerations for Human Study
2.5. Data Availability
3. Results
3.1. Comparison of the Number of Gastric Cancer Cases Between HBOC and Non-HBOC Families
3.2. Detection of Pathogenic Variants in BRCA1 and BRCA2 Genes in Gastric Cancer Tissues by Cancer Genome Panel Testing in a Population of Gastric Cancer Patients
3.3. Antitumor Efficacy and Adverse Events of the PARP Inhibitor Olaparib in Patients with HRD-Positive Gastric Cancer
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
Abbreviations
References
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Number of Patients with GC from Families with HBOC (Families n = 91) | Number of Patients with GC from Families Without HBOC (Families n = 94) | |||
---|---|---|---|---|
Generation | Patients with GC 2 (Other Types of Tumors 3) | Incidence (%) of GC 2 (Total Number of Patients) | Patients with GC 2 (Other Types of Tumors 3) | Incidence (%) of GC 2 (Total Number of Patients) |
I | 15 (26) | 4.36% (344) | 1 (6) | 0.31% (358) |
II | 47 (197) | 6.18% (761) | 6 (45) | 0.74% (730) |
III | 19 (145) | 3.24% (587) | 11 (42) | 1.73% (572) |
IV | 4 (12) | 0.99% (405) | 2 (7) | 0.55% (395) |
V | 1 (1) | 033% (299) | 0 (2) | 0.00% (281) |
VI | 0 (0) | 0.00% (28) | 0 (0) | 0.00% (41) |
Total cases | 86 (381) | 3.55% (2424) | 20 (102) | 0.84% (2377) |
Sex-wise distribution of patients with GC | ||||
Total cases | Patients with GC from families with HBOC (n = 86) | Patients with GC from families without HBOC (n = 20) | ||
64 men with GC | 74.41% men | 11 men with GC | 55.0% men with GC |
All Patients with GC | Patients with HRD-Positive GC * | |||
---|---|---|---|---|
Olaparib + PTX Group | Placebo + PTX Group | Olaparib + PTX Group | Placebo + PTX Group | |
Total number of cases | n = 67 | n = 65 | n = 35 | n = 33 |
Median PFS (months) | 4.92 | 3.25 | 5.39 | 3.59 |
HR | 0.81 95% CI: 0.61–1.04, p = 0.032 | 0.61 95% CI: 0.52–1.11, p = 0.067 | ||
Median OS (months) | 13.1 | 8.3 | 19.5 | 8.2 |
HR | 0.57 95% CI: 0.34–0.86, p = 0.010 | 0.36 95% CI: 0.16–0.72, p = 0.003 |
No. of Patients (%) | ||||||||
---|---|---|---|---|---|---|---|---|
All Patients with GC | Patients with HRD-Positive GC | |||||||
Olaparib/Paclitaxel Group (n = 67) | Placebo/Paclitaxel Group (n = 65) | Olaparib/Paclitaxel Group (n = 35) | Placebo/Paclitaxel Group (n = 33) | |||||
AEs | Any Grade | >Grade 3 | Any Grade | >Grade 3 | Any Grade | >Grade 3 | Any Grade | >Grade 3 |
Hematologic AEs | ||||||||
Anemia | 12 (18) | 7 (11) | 12 (19) | 7 (11) | 6 (17) | 3 (9) | 5 (17) | 3 (9) |
Neutropenia | 50 (75) | 31 (46) | 40 (65) | 25 (39) | 26 (74) | 6 (17) | (70) | 7 (21) |
Nonhematologic AEs | ||||||||
Alopecia | 31 (46) | 0 | 31 (47) | 0 | 15 (43) | 0 | 23 (40) | 0 |
Decreased appetite | 23 (34) | 0 | 27 (42) | 0 | 11 (32) | 0 | 5 (31) | 0 |
Peripheral neuropathy | 24 (36) | 2 (3) | 14 (21) | 1 (2) | 10 (31) | 0 | 8 (23) | 0 |
Nausea | 21 (31) | 0 | 26 (40) | 0 | 9 (26) | 8 (22) | 7 (22) | 6 (18) |
Asthenia | 20 (30) | 2 (3) | 18 (27) | 7 (10) | 10 (28) | 0 | 10 (20) | 0 |
Diarrhea | 21 (31) | 2 (3) | 18 (27) | 1 (2) | 11 (29) | 2 (6) | 7 (25) | 0 |
Abdominal pain | 15 (22) | 0 | 16 (24) | 2 (3) | 3 (21) | 0 | 1 (18) | 0 |
Fatigue | 16 (24) | 1 (10.4) | 21 (32) | 2 (3) | 3 (23) | 3 (9) | 6 (23) | 3 (9) |
Myalgia | 10 (15) | 0 | 23 (36) | 0 | 7 (13) | 2 (6) | 12 (36) | 3 (9) |
Pneumonia | 4 (6) | 2 (3) | 6 (9) | 3 (5) | 2 (6) | 1 (3) | 2 (6) | 1 (3) |
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Hayashi, T.; Sano, K.; Okada, M.; Muto, M.; Konishi, I. Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. Curr. Oncol. 2024, 31, 6723-6734. https://doi.org/10.3390/curroncol31110496
Hayashi T, Sano K, Okada M, Muto M, Konishi I. Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer. Current Oncology. 2024; 31(11):6723-6734. https://doi.org/10.3390/curroncol31110496
Chicago/Turabian StyleHayashi, Takuma, Kenji Sano, Mako Okada, Manabu Muto, and Ikuo Konishi. 2024. "Efficacy and Tolerability of Olaparib Plus Paclitaxel in Patients with Gastric Cancer Associated with Hereditary Breast and Ovarian Cancer" Current Oncology 31, no. 11: 6723-6734. https://doi.org/10.3390/curroncol31110496