Articles related to CLINICAL TRIALS

Memorial Sloan Kettering oncologist Raajit Rampal presents a case report, discusses the rationale for the few treatment options available, and summarizes the 5-year follow-up data for the RESPONSE and RESPONSE 2 trials.

This phase III trial evaluated the PARP inhibitor fuzuloparib versus placebo as a maintenance treatment after second- or later-line platinum-based chemotherapy in patients with high-grade, platinum-sensitive, recurrent ovarian cancer. Two-hundred-fifty-two (252) patients were randomly assigned to the fuzuloparib (n = 167) or placebo (n = 85). Twice daily oral fuzuloparib as maintenance therapy was superior to placebo in PFS improvement. Further, benefit was observed both in patients with germline BRCA 1/2 mutations and in those without mutations.

The poor showing for immunotherapy in PDAC is likely a result of the cancer’s complex immunosuppressive tumor microenvironment, acting to insulate the tumor against an effective cytotoxic immune response. This review summarizes the mechanisms of immunosuppression within the PDAC tumor microenvironment and provides an up-to-date review of completed and ongoing clinical trials using various immunotherapy strategies.

The 18-month OS rates in this trial were: 66.7% for neoadjuvant mFOLFIRINOX 47.3% for neoadjuvant mFOLFIRINOX and hypofractionated radiotherapy 87.5% for mFOLFIRINOX followed by pancreatectomy 78.9% for mFOLFIRINOX plus radiotherapy followed by pancreatectomy The authors state these results “suggest that mFOLFIRINOX represents a reference neoadjuvant treatment regimen for borderline resectable pancreatic cancer; however, the role of radiotherapy in this setting remains undefined.”

This paring of PARP inhibitor and immune checkpoint inhibitor may be a viable non-cytotoxic maintenance therapy option for patients with platinum-sensitive pancreatic ductal adenocarcinoma. At a median follow-up of 23.0 months, combining the PARP inhibitor niraparib with the anti CTLA-4 antibody ipilimumab achieved a 6-month PFS rate of 59.6%, which was superior to the comparator — a clinically meaningful benchmark of 44%. The results were not the same when a PD-1 inhibitor (nivolumab) were used. That trial arm yielded a poorer 6-month PFS vs the benchmark.

Even after allogeneic hematopoietic stem-cell transplant (HCT), poor outcomes are typically the case in patients with TP53-mutant (mTP53) acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS). The data from recent trials using the combination of eprenetapopt (APR-246) and azacitidine showed positive preclinical results in mTP53 AML/MDS, and this trial sought to assess the efficacy and safety of the eprenetapopt and azacitidine combination as maintenance therapy after allogeneic HCT in patients with mTP53 AML or MDS.