Another maintenance trial, NO statistically significant OS benefit but prolonged time to second-line chemotherapy. HR was favored Olaparib.
The phase III POLO study demonstrated significant progression-free survival (PFS) benefit for active olaparib maintenance therapy versus placebo for patients with metastatic pancreatic adenocarcinoma and a germline BRCA mutation. Here, we report the final analysis of overall survival (OS) and other secondary end points.
Patients with a deleterious or suspected deleterious germline BRCA mutation whose disease had not progressed after ≥ 16 weeks of first-line platinum-based chemotherapy were randomly assigned 3:2 to active maintenance olaparib (300 mg twice daily) or placebo. The primary end point was PFS; secondary end points included OS, time to second disease progression or death, time to first and second subsequent cancer therapies or death, time to discontinuation of study treatment or death, and safety and tolerability.
In total, 154 patients were randomly assigned (olaparib, n = 92; placebo, n = 62). No statistically significant OS benefit was observed (median 19.0 v 19.2 months; hazard ratio [HR], 0.83; 95% CI, 0.56 to 1.22; P = .3487). Kaplan-Meier OS curves separated at approximately 24 months, and the estimated 3-year survival after random assignment was 33.9% versus 17.8%, respectively. Median time to first subsequent cancer therapy or death (HR, 0.44; 95% CI, 0.30 to 0.66; P < .0001), time to second subsequent cancer therapy or death (HR, 0.61; 95% CI, 0.42 to 0.89; P = .0111), and time to discontinuation of study treatment or death (HR, 0.43; 95% CI, 0.29 to 0.63; P < .0001) significantly favored olaparib. The HR for second disease progression or death favored olaparib without reaching statistical significance (HR, 0.66; 95% CI, 0.43 to 1.02; P = .0613). Olaparib was well tolerated with no new safety signals.
Although no statistically significant OS benefit was observed, the HR numerically favored olaparib, which also conferred clinically meaningful benefits including increased time off chemotherapy and long-term survival in a subset of patients.
Somewhat disappointing as this was a negative study, however it is still an option for patients who are not candidates for mFOLFIRINOX.
Positive study for the combo of TMZ + cape vs. TMZ alone in met-pNET, confirming a regimen that is already widely used. Patients were first-line, and those with MGMT-def had a better response.
The NAPOLI-3 study assessed FOLFOX+ liposomal irinotecan vs. gemcitabine + nab-paclitaxel. NALIRIFOX was superior, with an OS of 11.1 vs. 9.2 months. Criticisms of modern gem trials are often that of rigid dosing requirements that differ from modern clinical practice. Additionally, it is unclear whether NALIRIFOX provides any meaningful benefit over FOLFIRINOX, and the cost is always a consideration.
Long term results on adjuvant FOLFIRINOX vs Gem in adjuvant pancreatic cancer. Although the survival benefit is quite significant (OS 53.5 vs 35.5 months respectively), I think the tell-tale numbers are the 5 year DFS being 26.1 vs 19%. The modest 7% curative benefit of triplet vs single agent chemotherapy highlights the difficulty in managing this disease and the continued need for investment in GI clinical trials.
Very interesting study which gives more support for preoperatory therapy in the setting of borderline resectable pancreatic cancer. The use of neodjuvant chemotherapy or chemoradiotherapy will likely increase overtime, as systemic options improve, even in pancreatic cancer. Optimal regimen is unknown as studies with other options such as Folfirinox, gemcitabine/albumin-bound paclitaxel are needed, post chemoradiotherapy.
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