Longer duration of adjuvant FOLFOX and atezolizumab was associated with improved DFS in a retrospective analysis of the ATOMIC trial.
Longer duration of adjuvant FOLFOX and atezolizumab (Tecentriq) was associated with improved disease-free survival (DFS) in patients with stage III deficient mismatch repair (dMMR) colon cancer, according to data from a retrospective, exploratory analysis of the phase 3 ATOMIC trial (A021502/AIO-KRK-0317; NCT02912559) presented during the
Among patients who received more than 6 cycles of FOLFOX, the addition of atezolizumab (n = 270) was associated with improved landmark DFS compared with FOLFOX alone (n = 235; adjusted HR, 0.45; 95% CI, 0.29-0.71). This association was not observed among patients who received 6 or fewer cycles of FOLFOX (n = 106; adjusted HR, 0.84; 95% CI, 0.35-2.01).
Patients who received at least 12 cycles of atezolizumab, encompassing combination therapy with FOLFOX and subsequent monotherapy (n = 270) had improved DFS vs those treated with FOLFOX alone (n = 46; adjusted HR, 0.48; 95% CI, 0.31-0.74). A similar trend was observed among patients who received fewer than 12 cycles of atezolizumab (n = 69), although this comparison did not reach statistical significance (adjusted HR, 0.59; 95% CI, 0.29-1.18).
“We still don’t know the optimal duration of therapy of FOLFOX or atezolizumab since this is an exploratory and retrospective analysis,” Anke Reinacher-Schick, director of the Clinic for Hematology and Oncology with Palliative Medicine at Katholisches Klinkum Bochum in Germany, said during the presentation. “However, [we saw] that more than 6 cycles of FOLFOX showed a DFS benefit when combined with atezolizumab but not with 6 cycles or less of FOLFOX.”
ATOMIC randomly assigned patients 1:1 to 6 months of modified FOLFOX6 (mFOLFOX6) plus atezolizumab followed by 6 months of atezolizumab monotherapy at 840 mg intravenously every 2 weeks or 6 months of mFOLFOX6 alone.1 Prior data from the study revealed that atezolizumab plus mFOLFOX6 significantly improved DFS in patient with stage III dMMR colon cancer.
In the retrospective, exploratory post-hoc analysis, investigators evaluated the association between treatment duration of FOLFOX or atezolizumab and DFS; duration varied because of toxicity and patient or investigator choice. A landmark analysis was used, restricted to patients who received at least 1 cycle of treatment and were free of disease progression or death at 12 cycles (6 months); DFS was landmarked at that time point and compared using log-rank tests, with HRs estimated from Cox models adjusted for T and N stage.
Two main analyses were performed: the association of FOLFOX duration (≤6 cycles vs >6 cycles) across the combination and FOLFOX-alone arms, and the association of atezolizumab duration, comprising combination therapy plus subsequent monotherapy (<12 cycles vs ≥12 cycles).
Baseline characteristics were balanced across both the FOLFOX (and atezolizumab (n = 611) duration analyses. Most patients were female (55.0%), had N1/N1c nodal status (62.5%), stage Tx/T1-3 disease (69.1%), and high-risk (T4 or N2) disease.
Within the FOLFOX plus atezolizumab arm, DFS was numerically better with more than 6 cycles of FOLFOX (n = 270) vs 6 or fewer cycles (n = 46; adjusted HR, 0.54; 95% CI, 0.25-1.17). Atezolizumab continuation after FOLFOX discontinuation occurred in 48% of patients who received 6 or fewer cycles of FOLFOX vs 87% of those who received more than 6 cycles.
A per-cycle modeling analysis showed a continuous DFS benefit with each additional cycle of FOLFOX in the combination arm (HR, 0.93; 95% CI, 0.84-1.03), an association that was not observed with FOLFOX alone (HR, 0.98; 95% CI, 0.91-1.05). Within the combination arm, DFS with 12 or more vs fewer than 12 cycles of atezolizumab produced an adjusted HR of 0.81 (95% CI, 0.38-1.71).
“The DFS benefit of atezolizumab plus FOLFOX increased continuously with an increasing number of FOLFOX cycles,” Reinacher-Schick said. “We can conclude that patients should continue FOLFOX and atezolizumab as long as they can tolerate it to obtain optimal benefit.”
Disclosures: Reinacher-Schick holds consulting or advisory roles with Amgen, Astra Zeneca, Pierre Fabre, and Roche. He also received Honoria from Amgen, Roche, and Takeda, as well as research funding from Arcus Bioscience, BioNTech, Genentech, Merck Healthcare, Rafael Pharmaceutics, Resilience, and Roche.
