Trifluridine/Tipiracil in Metastatic Colorectal Cancer: A UK Multicenter Real-world Analysis on Efficacy, Safety, Predictive and Prognostic Factors.

BACKGROUND: The orally administered combination trifluridine/tipiracil has been approved as third line treatment in mCRC, demonstrating survival benefit and acceptable toxicity profile in the phase III RECOURSE study. PATIENT AND METHODS: We performed a multicenter retrospective real-world analysis of patients with mCRC receiving trifluridine/tipiracil between 2016 and 2019 in eight cancer centers across the United Kingdom. RESULTS: A total of 236 patients were included with median age of 69 years. All patients had received at least 2 lines of fluoropyrimidine-based chemotherapy doublet with oxaliplatin or irinotecan. About 10% of patients had ECOG ≥ 2. Median duration of trifluridine/tipiracil treatment was 3 months with an ORR of 2.1% and disease control rate of 21.6%. Median OS was 7.6 and median PFS 3.3 months. A dose reduction was required in 27% of patients, while 7.6% discontinued treatment due to toxicity. The most common grade 3 toxicities were neutropenia (34%), fatigue (10%), anemia (9%) and febrile neutropenia (5%). Baseline NLR <5 and CEA <200 had favorable prognostic (HR: 0.52 and 0.39, P≤ .001) and predictive value (OR: 4.1 and 6.7, P< .05). Development of grade 3 neutropenia predicted treatment response (OR: 0.32, P< .001). Following treatment with trifluridine/tipiracil 41% were referred for phase I trial or rechallenged with chemotherapy. CONCLUSION: Trifluridine/tipiracil is well tolerated in refractory mCRC patients with comparable efficacy and toxicity profile to that of the phase III RECOURSE. Pretreatment NLR and CEA could serve as potential markers for patient selection, while treatment-induced grade 3 neutropenia predicted response. Prospective validation is needed.

The TICONC (Ticagrelor-Oncology) Study: Implications of P2Y12 Inhibition for Metastasis and Cancer-Associated Thrombosis.

BACKGROUND: In cancer, platelets may facilitate metastatic spread by a number of mechanisms as well as contribute to thrombotic complications. Ticagrelor, a platelet antagonist- that blocks adenosine diphosphate activation of platelet P2Y12 receptors, is widely used in the treatment of cardiovascular disease, but its efficacy in cancer remains unknown. OBJECTIVES: This study sought to evaluate the effect of aspirin and ticagrelor monotherapy, as well as dual antiplatelet therapy, on platelet activation in cancer. METHODS: This study consisted of 2 phases: first, an in vitro study of human platelet-tumor cell interaction; and second, a randomized crossover clinical trial of 22 healthy donors and 16 patients with metastatic breast or colorectal cancer. Platelet activation and inhibition were measured by aggregometry and flow cytometry. RESULTS: In vitro, tumor cells induced cellular clusters that were predominantly platelet-platelet aggregates. Ticagrelor significantly inhibited formation of large tumor cell-induced platelet-platelet aggregates: 65.4 ± 4.8% to 50.9 ± 5.9% (p = 0.002) and 62.3 ± 3.1% to 48.3 ± 7.3% (p = 0.014) for MCF-7 and HT-29-induced aggregation, respectively. Supporting this finding, cancer patients on ticagrelor had significantly reduced levels of spontaneous platelet aggregation and activation compared with baseline; 14.8 ± 2.7% at baseline to 7.8 ± 2.3% with ticagrelor (p = 0.012). CONCLUSIONS: Our findings suggested that P2Y12 inhibition with ticagrelor might reduce spontaneous platelet aggregation and activation in patients with metastatic cancer and merits further investigation in patients at high risk of cancer-associated thrombosis. (Ticagrelor-Oncology [TICONC] Study; EudraCT: 2014-004049-29).

A unique case of gliomatosis peritonei in a man, following a retroperitoneal teratoma.

We present an unusual case of a 56-year-old man presenting with abdominal swelling. Imaging revealed a large abdominal 23 cm cystic mass, which radiologically appeared to be related to the small bowel. There was an attempted surgical removal by the general surgeons. It was histologically confirmed as a retroperitoneal cystic teratoma with immature neural elements with incomplete resection margins. Residual disease was found at re-imaging 3 months later and a further block dissection was performed, with histology confirming recurrence. Thirteen months later, imaging revealed recurrent disease with peritoneal involvement. At laparoscopic exploration, there was peritoneal seeding, and biopsies confirmed a diagnosis of gliomatosis peritonei, secondary to the retroperitoneal teratoma. The patient proceeded to have combination chemotherapy to achieve stable disease on imaging. A month after completion, sadly, the disease progressed; the patient received best supportive care.