Lonsurf confirmed a numerical however not important enchancment in disease-free survival over placebo in sufferers with resected stage 4 colorectal most cancers.
Among the many full inhabitants of sufferers with colorectal most cancers (CRC) who had molecular residual illness after healing resection who had been enrolled to the part 3 ALTAIR examine, Lonsurf (trifluridine/tipiracil) didn’t lead to important enchancment in disease-free survival (DFS) over therapy with a placebo, however confirmed profit in sufferers with stage 4 illness.
Findings, which had been shared throughout the 2025 Gastrointestinal Cancers Symposium, confirmed that in all sufferers, the median DFS with Lonsurf (122 sufferers) was 9.3 months versus 5.55 months with placebo (121 sufferers), which translated to a numerical however not statistically important enchancment with Lonsurf. Furthermore, within the Lonsurf arm, the DFS charges at six, 12, 18 and 24 months had been 70.5%, 31.8%, 20.8% and 16.9%, respectively; within the placebo arm, these respective charges had been 45.5%, 26.8%, 21.5% and 14.5%.
Within the subgroup of sufferers with stage 4 illness, the good thing about Lonsurf (34 sufferers) was reported to be extremely pronounced versus placebo (32 sufferers), with a median DFS of 9.76 months and three.96 months, respectively. Within the Lonsurf arm, the six-, 12-, 18- and 14-month DFS charges had been 70.47%, 27.57%, 9.19% and 4.6%, respectively; within the placebo arm, these respective charges had been 31.25%, 12.5%, 3.12% and never reached.
“Total survival information had been immature, with solely 24 occasions noticed throughout each arms,” lead examine creator Dr. Hideaki Bando of the Division of Gastrointestinal Oncology on the Nationwide Most cancers Heart Hospital East in Kashiwa, Japan, and colleagues, wrote in a late-breaking poster spotlighting the information.
Glossary:
Illness-free survival (DFS): time with out most cancers after therapy.
Total survival: share of sufferers alive after therapy.
Metastasis: unfold of most cancers to different physique components.
Microsatellite-stable illness: no defects in DNA microsatellites.
Molecular residual illness: hint most cancers cells detected after remission.
Healing resection: surgical procedure to take away all tumor tissue for remedy.
Circulating tumor DNA (ctDNA): tumor DNA discovered within the blood.
Baseline MTM/mL: preliminary measurement of minimal tumor markers (MTM), that are biomarkers used to measure tumor presence or response to therapy in blood.
Extra Findings
“Baseline traits had been balanced between the 2 teams, and 96.3% of sufferers obtained standard-of-care therapy earlier than enrollment,” the examine authors wrote. In all sufferers, 64% had been youthful than 70 years, 58% had been male, 71% had left-sided colon as their main tumor website and 45% had stage 3 illness. Thirty-six % obtained neoadjuvant therapy, and 46% obtained adjuvant therapy. At one-month post-operation, 53% examined optimistic for circulating tumor DNA (ctDNA). Most sufferers had BRAF wild-type illness (96%), and 61% had RAS wild-type illness (61%). Ninety-eight % of sufferers had microsatellite-stable illness.
Extra efficacy findings had been reported for sufferers with non-stage 4 illness. On this group, the median DFS with Lonsurf was 9.26 months versus 6.05 months with placebo.
Furthermore, the baseline MTM/mL ranges proved to be considerably greater in sufferers with stage 4 illness versus non-stage 4 illness (0.68 versus 0.32). “The [Lonsurf] profit was considerably pronounced with greater MTM/mL, with linear profit noticed with rising MTM/mL values on the enrollment time level,” the examine authors underscored within the summary.
Concerning security, any-grade unintended effects occurred in 98.4% of sufferers within the Lonsurf arm versus 57% of these within the placebo arm; these results had been grade 3 (extreme) or worse for 73% and three.3% of sufferers, respectively. Severe unintended effects had been skilled by 4.9% of these within the Lonsurf arm; none occurred within the placebo arm. Uncomfortable side effects led to discontinuation for six.6% of sufferers within the Lonsurf arm. No unintended effects proved to be deadly in both arm.
Any-grade unintended effects associated to Lonsurf or placebo occurred in 98.4% and 33.1% of sufferers, respectively; they had been grade 3 or worse for 71.3% and 0.8% of sufferers, respectively. Just one severe treatment-related aspect impact was reported within the Lonsurf arm, and 5 treatment-related unintended effects led to discontinuation on this arm.
“No new security indicators had been recognized,” the examine authors wrote.
ALTAIR Background and Design
Testing ctDNA for molecular residual illness has confirmed to function a robust predictor for CRC recurrence, though the effectiveness of beginning systemic therapy to stop or delay recurrence in sufferers with molecular illness after healing surgical procedure stays an open query. With ALTAIR, investigators sought to find out the scientific relevance of leveraging Lonsurf as a pre-emptive remedy for sufferers who had been enrolled to the CIRCULATE-Japan examine and who had optimistic ctDNA following healing resection.
ALTAIR enrolled sufferers with CRC who obtained healing resection of main and/or metastatic websites with or with out customary adjuvant therapy and who prospectively examined ctNDA optimistic per the Signatera assay inside three months earlier than enrollment and didn’t expertise recurrence per CT imaging.
Sufferers had been then randomly assigned to obtain both Lonsurf or placebo at some point of six months. Investigators carried out CT and ctDNA analyses each two months for the primary 12 months and each three months for the second 12 months, adopted by further CT analyses each six months for the third 12 months. DFS served as the first finish level of the examine.
Of the 243 sufferers who had been registered within the trial, 122 had been included within the Lonsurf arm, and 121 had been included within the placebo arm; 72 and 59 sufferers, respectively, discontinued. Within the Lonsurf arm, the commonest cause for discontinuation was main illness relapse (34 sufferers), adopted by aspect impact (eight sufferers) and the deliberate begin date of the second course being set as the primary day of therapy and the beginning of the following course being delayed past the identical day of the week, 4 weeks later (eight sufferers).
Reference:
“A randomized, double-blind, part III examine evaluating trifluridine/tipiracil (FTD/TPI) versus placebo in sufferers with molecular residual illness following healing resection of colorectal most cancers (CRC): the ALTAIR examine.” By Dr. Dr. Hideaki Bando, et al. J Clin Oncol.
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