66 CHAPTER 3 Table 2. Serious Adverse Events (SAEs): 16 SAE’s occurred in 10 out of 27 patients. No grade ≥4 SAEs were reported. Grading according to Common Terminology Criteria for Adverse Events (CTCAE) 5.0. Abbreviations: GGT = gamma glutamyltransferase. SAE Grade ≥3 No % Dehydration 1 3.7 Fatigue 2 7.4 Enterocolitis 1 3.7 Hydronephrosis 1 3.7 GGT increased 2 7.4 Spinal cord compression 1 3.7 Pain 2 7.4 Pneumonitis 1 3.7 Tachycardia 1 3.7 Anemia 1 3.7 Dyspnea 2 7.4 Pulmonary embolism 1 3.7 DISCUSSION Precision medicine holds great promise for the future of patients with (advanced) cancer, but is hampered by many challenges, including target identification, prioritization and funding/ reimbursement of biomarker identification and treatment, due to extremely low numbers of patients with similar molecular profiles. This makes established methods of randomized trials to generate solid evidence for determination of treatment benefit difficult. To circumvent this challenge, the innovative design of the DRUP allows evaluation of small groups of patients with rare cancer subtypes to determine the potential benefit of a targeted agent in a group of patients with a specific tumor molecular profile. In patients with cancer harboring deleterious BRCA1/2 mutations, regardless of histological tumor type, we here report that olaparib monotherapy is an effective and tolerable treatment option, for both germline and somatic alterations. The majority of patients (58%) derived CB from olaparib treatment. CB was almost exclusively observed in patients who had bi-allelic BRCA LoF and a high HRD-score, confirming the absence of a functional homologous repair system. Post hoc selection of only those patients with confirmed bi-allelic loss of BRCA1/2 (N=15) revealed a CBR of 73% (N=11). A considerable proportion of patients in this cohort had BRCA-associated tumor types (i.e. prostate , ovarian, breast and pancreatic cancer), of which we now know that olaparib is an effective treatment option49-53. Ten out of 15 evaluable patients with BRCA-associated histolo-
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