No benefit of additional oxaliplatin in elderly patients with mCRC

Elderly patients with metastatic colorectal cancer (mCRC) did not benefit from the addition of oxaliplatin to the first-line standard-of-care fluoropyrimidine plus bevacizumab treatment regimen. In addition, patients treated with additional oxaliplatin experienced a higher grade of toxicity. Therefore, the authors recommend the omission of oxaliplatin during the initial treatment of elderly patients with mCRC [1].

“Fluoropyrimidine plus oxaliplatin with bevacizumab is a first-line standard-of-care option for patients with mCRC,” said Dr Tetsuya Hamaguchi (National Cancer Center, Japan). “However, elderly patients are under-represented in clinical trials investigating potential therapies for mCRC. The JCOG1018 RESPECT study (UMIN000008866) assessed the effect of added oxaliplatin to standard-of-care regimens in elderly patients (≥70 years) with unresectable mCRC. Patients in the ‘no oxaliplatin’ arm (n=125) received a 5-fluorouracil and low-dose leucovorin plus bevacizumab regimen or a capecitabine plus bevacizumab regimen. Patients in the ‘added oxaliplatin’ arm (n=126) received one of the same regimens plus oxaliplatin: 85 mg/m² (mFOLFOX) or 130 mg/m² (CapeOX), every 2 weeks. The primary endpoint was progression-free survival (PFS).

The addition of oxaliplatin did not lead to a significantly prolonged median PFS compared with the regimens that omitted oxaliplatin (10.0 vs 9.4 months; HR 0.837; one-sided P=0.086). However, subgroup analyses suggested that patients with wildtype RAS status may benefit from added oxaliplatin (median PFS 11.0 months) compared with no oxaliplatin (9.6 months; HR 0.578) (see Figure). Furthermore, the overall survival analysis displayed no survival benefit of added oxaliplatin over no oxaliplatin (median 19.7 vs 21.3 months) in the study population.

Figure: Subgroup analyses of PFS in JCOG1018 [1]



CI, confidence interval; ECOG PS, ECOG performance status; HR, hazard ratio; mPFS, median progression-free survival; OX, oxaliplatin.

The safety analysis discouraged the addition of oxaliplatin to standard treatment regimens in this population. The addition of oxaliplatin resulted in a higher rate of grade 3–4 neutropenia (24% vs 15%) and higher rates of grade 2–4 nausea (22% vs 10%), diarrhoea (16% vs 7%), fatigue (32% vs 21%), and sensory neuropathy (57% vs 15%).

These data are in concordance with the PANDA trial favouring first line 5-fluoroacil + panitumumab versus FOLFOX + panitumumab in elderly RAS wildtype mCRC and the AVEX trial in favour of capecitabine + bevacizumab [2,3].

1. Hamaguchi T, et al. A randomized phase 3 trial of mFOLFOX7 or CapeOX plus bevacizumab versus 5-FU/l-LV or capecitabine plus bevacizumab as initial therapy in elderly patients with metastatic colorectal cancer: JCOG1018 study (RESPECT). Abstract 10, ASCO GI 2022, 20–22 January.


2. Lonardi S, et al. Abstract 4002, ASCO Annual Meeting 2020, 29–31 May.


3. Cunningham D, et al. Lancet Oncol. 2013 Oct;14(11):1077-1085.

 

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Posted on 21 March, 202221 March, 2022