Reduced-dose S1 + oxaliplatin combo therapy preserves QoL in older patients with mCRC

The combination of reduced-dose S1 and oxaliplatin (SOx) chemotherapy preserves quality of life (QoL) and physical function in vulnerable older patients with metastatic colorectal cancer (mCRC), according to a subgroup analysis of the NORDIC9* study presented at ESMO GI 2021.

“Older patients with incurable cancer often tend to prioritize improvement or preservation of QoL and other patient-centred outcomes, rather than survival … [Therefore, we aim to] investigate whether increased efficacy with SOx, [as shown in the primary analysis of the NORDIC9* study,] comes at the expense of poorer QoL and physical functioning,” said lead author Dr Gabor Liposits from the Department of Oncology at Odense University Hospital in Odense, Denmark.

This investigator-initiated study included 150 older patients (median age 78 years) with mCRC who were not considered eligible for full-dose combination chemotherapy. Participants were randomly assigned in a 1:1 ratio to receive either reduced-dose SOx** combination chemotherapy or full-dose S1*** monotherapy. EORTC QLQ-C30 questionnaire was used to assess global QoL and physical functioning. [ESMO GI 2021, abstract SO-15]

At 9 weeks, patients treated with reduced-dose SOx combination chemotherapy demonstrated a favourable change in global QoL, indicating better QoL, compared with full-dose S1 monotherapy (2.63 vs -4.22; p=0.127). “Despite this being nonsignificant, the  [between-group]  difference exceeded the prespecified threshold for minimally important differences (MIDs),” said Liposits.

A statistically significant improvement in the physical functioning domain at 9 weeks was observed favouring the reduced-dose SOx group vs the full-dose S1 group (-0.14 vs -7.52; p=0.03), which also exceeded the prespecified threshold for between-group MID, Liposits noted.

With regard to symptom domain, a statistically significant between-group difference was observed in both the SOx and S1 groups for dyspnoea (-3.08 vs 8.27; difference, -11.36; p=0.024), but not with fatigue domain (2.62 vs 7.88; difference, -5.26; p=0.281), which did not exceed the threshold for clinical relevance at week 9.

“[Overall,] the NORDIC9 study established that reduced-dose [SOx] combination chemotherapy in addition to its increased efficacy did not result in inferior QoL compared with the reference treatment with full-dose [S1] monotherapy in older patients not fit for standard combination treatment,” said Liposits.

“[Therefore,] we recommend reduced-dose [SOx] combination chemotherapy in vulnerable older patients with mCRC as it resulted in preserved [global] QoL and physical functioning, improved efficacy in form of significantly prolonged PFS, and less[er] toxicities and hospitalizations compared to full-dose [S1] monotherapy,” he added.

*NORDIC9: Full dose S-1 monotherapy compared to reduced dose S-1/oxaliplatin combination therapy as first-line treatment for older patients with metastatic colorectal cancer

**Reduced-dose SOx: S1 20 mg/m² orally twice daily on days 1–14 + oxaliplatin 100 mg/m² intravenously on day 1 Q3W