The addition of aflibercept to FOLFIRI has been demonstrated to improve survival in patients with metastatic colorectal cancer (mCRC) who progressed after receiving a standard oxaliplatin-based ...regimen. In this retrospective, single-institution, observational study we collected clinical data from mCRC patients who received aflibercept in combination with FOLFIRI in routine clinical practice from October 2012 to March 2021 to describe feasibility and efficacy of this regimen in a real-world population. Forty-nine patients receiving aflibercept-FOLFIRI as second-line treatment were identified, 40.8% of whom were aged over 65 years. The majority of patients had multi-organ metastases (73.5%), and had previously received bevacizumab in combination with chemotherapy (CT) as first-line treatment (79.6%). Median overall survival (OS) and progression-free survival (PFS) were 13 and 6 months, respectively; overall response rate (ORR) and disease control rate (DCR) were 12.3% and 49.1%, respectively. Several factors were associated with survival in univariate analysis, including PFS in first-line therapy, number of metastatic sites, bone metastases and others. However, in multivariate analysis, only PFS in first-line CT over 12 months was significantly associated with better OS (HR 0.32; 95% CI 0.13–0.79; p = 0.01). Hypertension was the most commonly reported grade (G) 3–4 adverse event (AE), affecting 18.4% of the overall population. Thromboembolic events were observed in 16.3% of patients, hemorrhagic events in 10.2%, and proteinuria in 8.2%. Neutropenia was the most frequently observed hematological G3–4 AE with an incidence of 10.2%. Aflibercept-FOLFIRI has been confirmed as a feasible second-line treatment for mCRC in a re-al-life setting, and PFS in first-line therapy >12 months resulted as the only predictive marker of better survival.
The incidence of myeloid neoplasms following treatment with poly (ADP-ribose) polymerase inhibitors (PARPi) in patients with ovarian cancer has been gradually increasing over the last few years. The ...cumulative exposure to PARPi and the improved overall survival of patients with ovarian cancer may represent key underlying explanations behind such trend. Fortunately, the earlier introduction of PARPi in the frontline setting reduces the risk of developing secondary myeloid neoplasms. The etiopathogenesis is still unclear but is likely to be multifactorial. The first 2 years of PARPi exposure seem to be the critical window for the onset of myeloid neoplasms post PARPi, with persistent cytopenia recognized as an early warning sign. Despite intensive treatment strategies, the outcome remains poor. There is an unmet clinical need to learn how to minimize risk, make an early diagnosis, and manage myeloid neoplasms post PARPi. First, decision making regarding the optimal maintenance treatment should avoid a 'PARPi-for-all' strategy. PARPi should be used cautiously in cases of high baseline risk for myeloid neoplasms and/or patients who are less likely to have a benefit. Active surveillance, accurate differential diagnosis, and prompt hematological referral are key management pillars. This review discusses what is known on this emerging issue as well as unresolved questions.
TPS5628 Background: PAOLA-1/ENGOT-ov25 trial demonstrated that Olaparib (O) plus Bevacizumab (B) determined a significant survival benefit in patients (pts) with advanced, high-grade, epithelial ...ovarian, peritoneal and/or fallopian-tube cancer (HEOC) presenting defects of homologous recombination repair system (HRD+) in clinical response after first-line platinum-based chemotherapy (CT) plus B. Methods: IOLANTHE is a multicenter Italian phase IV trial (sponsored by the MaNGO group, Protocol Number IRFMN-OVA-8542) aiming to confirm in a setting close to clinical practice the efficacy of this combination in pts with HRD+HEOC. As the study includes a consistent translational component, all suspicious advanced cases will be considered for study enrollment. Pts with a confirmed pathological diagnosis of HEOC will be included in the step 1 of the trial which main inclusion criteria are the following: -availability of formalin-fixed, paraffin-embedded samples for the central testing of HRD status (performed by Myriad Mychoice CDx Plus assay) - suitability to receive CT + B. Only HRD+ pts responding to first line CT plus at least one cycle of B will be enrolled in the step 2 of the trial and will be treated with B 15 mg/kg every 3 weeks plus O 300 mg twice daily. Considering the PAOLA-1 median progression free survival (PFS) of 37.2 months (mo) in the B-O arm, with a sample size of 90 pts followed for 24 months and setting a one-side error of 5%, we will have a statistical power of 80% to demonstrate a PFS-24mo≥64% with an upper critical value of 61%. In order to have 90 patients eligible for the step 2 of the study, 190 pts are needed to be enrolled in the step 1 of the clinical study (as approximately 80% of pts with HEOC will respond to CT and out of these, 60% will be HRD+). The translational subproject 1 will consist of the analysis of circulating-tumor (ctDNA), using whole genome sequencing aiming - to correlate residual tumour after surgery and ctDNA levels - to anticipate the diagnosis of progression - to monitor the mutational status of HR-related genes and other genes such as Tp53BP1, POLQ, REV7 probably involved in PARPi resistance during the maintenance therapy. The translational subproject 2 will be developed to compare pts’ response to therapy with that of cancer cells, tested by organotypic model treated with the combination. These models will be generated using fresh tumor tissue and ascitic fluid for the isolation of the tumor cells and macroscopically healthy omentum for the isolation of the mesothelial cells and fibroblasts. Eight centers have been activated and other 6 are waiting for the activation with 19 patients registered and 3 screening failures. The enrollment is continuing, according to protocol timeline (12 months for enrollment, 6 months for surgery and CT and 24 months for maintenance treatment). Clinical trial information: NCT06121401 .
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