KEY TAKEAWAYS
- The phase 1 NOW trial assessed the feasibility of using olaparib in the neoadjuvant context for patients with advanced, high-grade, BRCA-mutant ovarian cancer.
- The median number of olaparib cycles was 2, while the median number of chemotherapy cycles was 6.
- The study demonstrated that neoadjuvant olaparib treatment was well tolerated in BRCA-mutant ovarian, peritoneal, or fallopian tube cancer.
The phase 1 NOW trial’s primary objective was to ascertain the feasibility of administering olaparib in the neoadjuvant setting for patients (pts) diagnosed with advanced, high-grade, BRCA-mutant ovarian cancer. Secondary objectives encompassed evaluating the drug’s effectiveness, the proportion of patients suitable for interval tumor reduction surgery, complete pathological response, and toxicity.
Inclusion criteria for patient enrollment consisted of having a germline BRCA1/2, RAD51C/D, or PALB2 mutation; exhibiting high-grade serous histology; being eligible for neoadjuvant chemotherapy followed by planned interval tumor reduction surgery; having measurable or evaluable disease; and not having undergone prior treatment. Additional criteria encompassed an ECOG performance status between 0 and 2; adequate functioning of normal organs and bone marrow; hemoglobin levels at or above 9; an absolute neutrophil count above 1.5; a platelet count above 100; bilirubin levels at or below 1.5; aspartate/alanine aminotransferase levels at or below 2.5 times the upper limit of normal; and a creatinine clearance rate at or above 40 ml/min.
Among a total of 61 screened patients, 51 patients underwent genetic testing. Out of these, 20 were found to have the specified mutations, and 15 patients were administered olaparib. As per the study protocol, olaparib was administered in the neoadjuvant setting. Patients experiencing disease progression or non-surgical amenable responses proceeded to receive chemotherapy with paclitaxel and carboplatin, followed by surgery, additional chemotherapy, and maintenance with PARP inhibitors. Patients with favorable responses to neoadjuvant olaparib underwent surgery, followed by chemotherapy and PARP inhibitor maintenance at the discretion of the investigator.
The median number of olaparib cycles stood at 2 (range: 2-2), while the median number of chemotherapy cycles was 6 (range: 0-6). Among the 13 patients with evaluable data, a partial response was observed in 53.8% of cases. The majority of patients (86.6%) proceeded to surgery immediately after olaparib treatment, with 6.7% forgoing surgery entirely and another 6.7% undergoing interval surgery after chemotherapy. Out of the patients who underwent surgical debulking (n = 14), a significant portion (85.7%) achieved optimal results with no detectable remaining disease. The remaining patients achieved optimal resection with residual disease measuring less than 1 cm. In terms of adjuvant therapy, patients received paclitaxel/carboplatin for 6 cycles (n = 7), 4 cycles (n = 1), or 3 cycles (n = 3). The cycle number for one patient was pending during analysis, and 3 patients transitioned to a PARP inhibitor instead of chemotherapy. One patient who underwent adjuvant chemotherapy exhibited chemotherapy-resistant progression, and another patient experienced a deterioration in performance status during chemotherapy. Furthermore, 93% of patients demonstrated a 25% reduction in CA125 levels, 87% exhibited a 50% reduction, and 73% showcased a 75% reduction. The median best percentage change was 81% (range: -98.1% to 35%).
In terms of safety, commonly encountered adverse effects included abdominal distention (6.7% of all cases; n = 1), abdominal pain (33.3% of all cases; n = 5), anemia (20% of all cases; n = 3; grade 3/4, n = 3), anorexia (6.7% of all cases), back pain (6.7% of all cases), constipation (26.7% of all cases; n = 4), dyspnea (6.7% of all cases), fatigue (6.7% of all cases), nausea (13.3% of all cases; n = 2), and pain (13.3% of all cases). Dosing interruption occurred in 1 patient, and another patient underwent a dose reduction of olaparib due to grade 3 anemia.
The administration of olaparib as a neoadjuvant therapy before surgical resection and adjuvant chemotherapy was well received in pts recently diagnosed with ovarian, peritoneal, or fallopian tube cancer bearing BRCA mutations.
Source: https://sgo.planion.com/Web.User/SesDetACCOUNT=SGO&CONF=AM2023&USERPID=PUBLIC&SCHEDID=285312
Clinical Trial: https://classic.clinicaltrials.gov/ct2/show/NCT03943173
Westin, S.N.
