Dataset Information

Pooled safety analysis from phase III studies of trifluridine/tipiracil in patients with metastatic gastric or gastroesophageal junction cancer and metastatic colorectal cancer

ABSTRACT:

Background

Trifluridine/tipiracil (FTD/TPI) showed clinical benefit, including improved survival and manageable safety in previously treated patients with metastatic colorectal (mCRC) or gastric/gastroesophageal junction (mGC/GEJC) cancer in the phase III RECOURSE and TAGS trials, respectively. A pooled analysis was conducted to further characterize FTD/TPI safety, including management of haematologic toxicities and use in patients with renal or hepatic impairment.

Patients and methods

Adults with ≥2 prior regimens for advanced mGC/GEJC or mCRC were randomized (2 : 1) to FTD/TPI [35 mg/m2 twice daily days 1-5 and 8-12 (28-day cycle); same dosage in both trials] or placebo plus best supportive care. Adverse events (AEs) were summarized in the safety population (patients who received ≥1 dose) and analysed by renal/hepatic function.

Results

TAGS and RECOURSE included 335 and 533 FTD/TPI-treated and 168 and 265 placebo-treated patients, respectively. Overall safety of FTD/TPI was similar in TAGS and RECOURSE. Haematologic (neutropenia, anaemia) and gastrointestinal (nausea, diarrhoea) AEs were most commonly observed. Laboratory-assessed grade 3-4 neutropenia occurred in 37% (TAGS)/38% (RECOURSE) of FTD/TPI-treated patients (median onset: 29 days/55 days), and 96% (TAGS)/97% (RECOURSE) of cases resolved regardless of renal/hepatic function. Supportive medications for neutropenia were received by 17% (TAGS) and 9% (RECOURSE); febrile neutropenia was reported in 2% and 4%, respectively. Overall grade ≥3 AEs were more frequent in patients with moderate renal impairment [81% (TAGS); 85% (RECOURSE)] versus normal renal function (74%; 67%); anaemia and neutropenia were more common in patients with renal impairment. FTD/TPI safety (including haematologic AEs) was consistent across patients with normal and mildly impaired hepatic function.

Conclusions

These results support FTD/TPI as a well-tolerated treatment in patients with mGC/GEJC or mCRC, with a consistent safety profile. Safety was largely similar in patients with normal or mildly impaired renal/hepatic function; however, patients with renal impairment should be monitored for haematologic toxicities. Highlights • This pooled safety analysis shows a consistent safety profile of FTD/TPI in patients with mCRC and mGC/GEJC.• Haematologic and gastrointestinal adverse events (AEs) were the most common types of AEs with FTD/TPI treatment.• FTD/TPI was well tolerated; AEs were managed well with dosing modifications and supportive medications.• The FTD/TPI safety profile was similar in patients with normal or mildly impaired renal or hepatic function.• Patients with renal impairment should be carefully monitored for haematologic toxicities.

SUBMITTER: Van Cutsem E

PROVIDER: S-EPMC9808443 | biostudies-literature | 2022 Nov

REPOSITORIES: biostudies-literature

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Project description:BackgroundIn the phase III TAGS trial, trifluridine/tipiracil showed survival benefit versus placebo in patients with metastatic gastric/gastroesophageal junction cancer and ≥ 2 prior chemotherapies. This post hoc exploratory analysis assessed the impact of prior therapy type on outcomes.MethodsBased on prior treatment, patients in TAGS (N = 507) were categorized into overlapping subgroups: ramucirumab ± other agents (n = 169), no ramucirumab (n = 338), paclitaxel but no ramucirumab (n = 136), ramucirumab + paclitaxel sequentially or in combination (n = 154), neither paclitaxel nor ramucirumab (n = 202), irinotecan (n = 281), and no irinotecan (n = 226). Overall and progression-free survival, time to Eastern Cooperative Oncology Group performance status (ECOG PS) ≥ 2, and safety were assessed.ResultsBaseline characteristics and prior therapy patterns were generally well balanced between trifluridine/tipiracil and placebo arms across subgroups. Trifluridine/tipiracil was associated with survival benefits versus placebo regardless of prior treatment: across subgroups, median overall survival was 4.6-6.1 versus 3.0-3.8 months (hazard ratios, 0.47-0.88), median progression-free survival was 1.9-2.3 versus 1.7-1.8 months (hazard ratios, 0.49-0.67), and median time to ECOG PS ≥ 2 was 4.0-4.7 versus 1.9-2.5 months (hazard ratios, 0.56-0.88). Among trifluridine/tipiracil-randomized patients, median overall and progression-free survival trended longer in those who had not received ramucirumab, paclitaxel and ramucirumab, or irinotecan (6.0-6.1 and 2.1-2.3 months, respectively) than in those who previously received these agents (4.6-5.7 and 1.9 months). The trifluridine/tipiracil safety profile was consistent across subgroups, with similar overall incidences of grade ≥ 3 adverse events. Minor variations in hematologic toxicities were noted.ConclusionsIn TAGS, third- or later-line trifluridine/tipiracil treatment demonstrated overall and progression-free survival and functioning benefits versus placebo and a consistent safety profile in patients with metastatic gastric/gastroesophageal junction cancer, regardless of prior treatment type.Clinical trials registrationclinicaltrials.gov NCT02500043.