Panitumumab beats bevacizumab in RAS wildtype left-sided metastatic colorectal cancer  

Panitumumab was superior to bevacizumab when added to mFOLFOX6 as first-line therapy in patients with RAS wildtype metastatic colorectal cancer (mCRC), especially in patients with left-sided tumours. The results of the phase 3 PARADIGM trial support mFOLFOX6 plus panitumumab as first-line therapy in patients with RAS wildtype left-sided mCRC. 

Adding an EGFR inhibitor or VEGF inhibitor to chemotherapy improves the overall survival (OS) of patients with mCRC significantly [1]. In patients with RAS wildtype, left-sided, colorectal tumours, the benefit of an EGFR inhibitor may be enriched, based on retrospective analysis [2]. The phase 3 PARADIGM trial assessed this matter by randomising 823 patients with RAS wildtype mCRC 1:1 to mFOLFOX6 plus the EGFR inhibitor panitumumab or to mFOLFOX6 plus the VEGF inhibitor bevacizumab [3]. In total, 604 patients had left-sided tumours. The primary endpoints of this trial were OS in the left-sided population and OS in the overall population. Dr Takayuki Yoshino (National Cancer Center Hospital East, Japan) presented the results.

After 5 years of follow-up, panitumumab performed better than bevacizumab in terms of median OS in both the left-sided population (37.9 vs 34.3 months; HR 0.82; P=0.031; see Figure) and the overall population (36.2 vs 31.3 months; HR 0.84; P=0.030). The OS curves of the 2 treatment regimens separated after 28 months. In contrast, the median progression-free survival did not differ between treatment regimens: left-sided population (13.7 vs 13.2 months; HR 0.98); overall population (12.9 vs 12.0 months; HR 1.01). According to Dr Yoshino, the research group expected this result. Other efficacy outcomes favoured the panitumumab arm, especially in the left-sided sub-population, in whom response rates were 80.2% versus 68.6%. Interestingly, an exploratory analysis of OS in the right-sided population did not display a benefit of panitumumab over bevacizumab (20.2 vs 23.2 months; HR 1.09).

Figure: Overall survival of panitumumab versus bevacizumab in left-sided population [3]



No new safety issues were observed for the treatment regimens. In the panitumumab arm, 71.8% of the patients experienced grade ≥3 adverse events compared with 64.9% of the patients in the bevacizumab arm. The treatment discontinuation rates due to adverse events were 23.8% and 18.4% in the panitumumab arm and bevacizumab arm, respectively. Acne-like dermatitis, paronychia, dry skin, and hypomagnesaemia were more often observed in patients on panitumumab.

“These results support panitumumab plus mFOLFOX6 as first-line therapy for patients with RAS wildtype and left-sided mCRC,” concluded Dr Yoshino. “A large-scale biomarker analysis is currently ongoing (NCT02394834) to gain in-depth understanding of these results.”

1. Venook AP, et al. JAMA. 2017;317(23):2392‒2401. 
2. Arnold D, et al. Ann Oncol. 2017; 28(8):1713‒1729. 
3. Yoshino T, et al. Panitumumab (PAN) plus mFOLFOX6 versus bevacizumab (BEV) plus mFOLFOX6 as first-line treatment in patients with RAS wild-type (WT) metastatic colorectal cancer (mCRC): Results from the phase 3 PARADIGM trial. LBA1, ASCO 2022 Annual Meeting, 3–7 June, Chicago, IL, USA.

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Posted on 5 August, 202228 March, 2024