First-line panitumumab improves metastatic-site resection rates in RAS wild-type mCRC

At the European Society for Medical Oncology (ESMO) Asia Congress 2025 in Singapore, results of a retrospective cohort study that evaluated first-line panitumumab- vs cetuximab-based therapy in patients with newly diagnosed RAS wild-type metastatic colorectal cancer (mCRC) were reported. The analysis focused on overall survival (OS) and metastatic-site resection rates, providing valuable real-world insights into treatment selection beyond traditional survival endpoints.

First-line panitumumab vs cetuximab
The multicentre retrospective cohort study included 687 patients diagnosed with RAS wild‑type mCRC between 2018 and 2022 who were treated with first‑line chemotherapy in combination with EGFR monoclonal antibodies (mAb), panitu­mumab (n=229) or cetuximab (n=458), across four medical centres in Taiwan. The patients were followed up until December 2023. Baseline characteristics after pro­pensity score matching (1:2) were well balanced across key variables, including age, primary tumour site, tumour sided­ness, and prior colectomy, with approx­imately 90 percent of patients having left‑sided primary tumours. [Chang PH, et al, ESMO Asia 2025, abstract 235eP]

In the overall matched cohort, me­dian OS was similar between the pa­nitumumab and cetuximab groups (30.9 vs 28.3 months; hazard ratio [HR], 0.94; p=0.705), confirming similar long‑term survival outcomes with either mAb used as the first‑line biologic part­ner in this patient population. A similar pattern was observed in the left‑sided subgroup (median OS, 30.9 vs 27.5 months; HR, 0.76; p=0.078), with a numerical but not statistically significant advantage for panitumumab.

Panitumumab: Higher metastatic-site resection rates
Metastatic-site resection rates, de­fined as curative-intent resection of liver/ lung metastases, showed a consistent and clinically meaningful advantage for panitumumab.

In the overall cohort, panitumumab was associated with higher liver and lung resection rates vs cetuximab (liver resec­tion: 22.5 vs 13.4 percent; odds ratio [OR], 1.88; 95 percent confidence interval [CI], 1.23–2.89; p=0.004) (lung resection: 9.0 vs 3.0 percent; OR, 3.21; 95 percent CI, 1.57–6.59; p=0.001). When liver or lung resection was considered together, the proportion of patients achieving curative‑intent resection at either site was 26.0 percent with panitumumab vs 14.4 per­cent with cetuximab (OR, 2.09; 95 per­cent CI, 1.41–3.11; p<0.001). (Figure 1)

Similar results were observed in fa­vour of panitumumab vs cetuximab in the left-sided cohort, with liver resection rates of 22.5 vs 16.1 percent (OR, 1.51; 95 per­cent CI, 1.01–2.27; p=0.046), lung resec­tion rates of 8.8 vs 4.1 percent (OR, 2.24; 95 percent CI, 1.19–4.22; p=0.013), and liver or lung resection rates of 25.7 vs 17.1 percent (OR, 1.68; 95 percent CI, 1.16– 2.45; p=0.007). (Figure 1)

Prognostic impact of metastatic-site resection
The consistently higher probabilities of metastatic‑site resection with panitu­mumab vs cetuximab for liver, lung and combined metastatic resections under­line a clinically relevant advantage that persists despite comparable OS between the treatment arms.

Importantly, metastatic-site resec­tion had a prognostic impact. In the overall cohort, patients who underwent metastatic‑site resection had signifi­cantly longer OS than those who did not (54.9 vs 22.1 months; p<0.001). (Figure 2) Similarly, in the left‑sided co­hort, metastatic‑site resection translat­ed into an OS of 54.9 months vs 24.2 months for patients without metastatic-site resection. These results indi­cate that conversion to resectability may more than double the OS in this population.

These data support first‑line use of panitumumab when clinical goals in­clude downstaging liver or lung metas­tases to enable curative‑intent surgery, particularly in patients with newly diagnosed RAS wild‑type mCRC.

Taiwan national data: Anti‑EGFRs vs bevacizumab
Complementary evidence from a nationwide claims‑linked registry in Taiwan further supports prioritizing anti‑EGFR agents over anti‑VEGF ther­apy as first‑line biologics in left‑sided RAS wild‑type mCRC when conversion surgery is a key endpoint. [Chang PH, et al, ESMO Asia 2025, abstract 235eP; Ann Coloproctol 2025;41:462-472]

Using Taiwan’s National Health Insurance Database and the Taiwan Cancer Registry, this retrospective co­hort study analyzed data from 4,849 patients with unresectable KRAS wild‑type mCRC treated with ≥6 cycles of bevacizumab, cetuximab, or panitu­mumab between 2011 and 2021. The study used inverse probability overlap weighting to balance extensive clinicopathologic and treatment covariates. [Ann Coloproctol 2025;41:462-472]

Advantages of anti-EGFRs
Unadjusted median OS was longer with panitumumab and cetuximab (817 and 748 days, respectively) vs bevaci­zumab (636 days). (Figure 3)

Results remained consistent after ad­justment, demonstrating that treatment with either panitumumab or cetuximab was associated with improved OS vs bevacizumab in the overall population (adjusted HR for panitumumab vs beva­cizumab, 0.76; 95 percent CI, 0.65–0.88; p<0.001) (adjusted HR for cetuximab vs bevacizumab, 0.81; 95 percent CI, 0.73– 0.90; p<0.001), with no significant differ­ence in OS between the two anti‑EGFR agents (adjusted HR, 0.93; 95 percent CI, 0.79–1.10; p=0.395). [Ann Coloproctol 2025;41:462-472]

In the left‑sided subgroup, survival gains with anti‑EGFR therapy were even more pronounced: adjusted HRs for OS vs bevacizumab were 0.75 (95 percent CI, 0.64–0.89) for panitumumab and 0.77 (95 percent CI, 0.68–0.86) for cetuximab (both p<0.001), while no OS differences were observed among the three biolog­ics in right‑sided disease. Importantly, both panitumumab and cetuximab were associated with significantly higher rates of conversion for surgery than bevaci­zumab (adjusted HR for conversion, 2.22 [95 percent CI, 1.76–2.81] and 1.73 [95 percent CI, 1.42–2.10], respectively; both p<0.001), with panitumumab again showing a stronger association. [Ann Col­oproctol 2025;41:462-472]

These findings mirror the conversion advantage seen in the previous multi­centre cohort and reinforce the biological rationale for EGFR blockade in patients with left‑sided RAS wild‑type mCRC, where EGFR pathway activation and che­mosensitivity may be greater. [Chang PH et al, ESMO Asia 2025, abstract 235eP; Ann Coloproctol 2025;41:462-472]

HK real‑world experience with mCAPIRI‑P regimen
Real‑world data from a retrospec­tive study in Tuen Mun Hospital, Hong Kong, offer additional evidence for panitumumab‑containing regimens as effective first‑line options in pa­tients with RAS wild‑type advanced CRC and underscore its particular strength in conversion resection of liver‑only metastases. The cohort includ­ed 106 consecutive patients with RAS wild‑type, unresectable locally ad­vanced or mCRC who received first‑line modified capecitabine, irinotecan and panitumumab (mCAPIRI‑P) between July 2019 and December 2021. The regimen used 3‑weekly cycles of oral capecitabine 800 mg/m² BID on days 1–14, and intravenous irinotecan 200 mg/m² plus panitumumab 9 mg/kg on day 1, with treatment continued until progression or planned drug holidays. [Front Oncol 2023;13:1138357]

First-line efficacy and safety
Median progression‑free survival on treatment (PFSOT) was 15.4 months and median OS was 25.5 months with the mCAPIRI‑P regimen – out­comes comparable to those of land­mark trials evaluating anti‑EGFR agents plus doublet chemotherapy with 5‑fluoruracil–based backbones. [Front Oncol 2023;13:1138357; Ann Oncol 2014;25:1346-1355; J Clin Oncol 2019;37:3401-3411; Yoshino T, et al, ASCO 2022, abstract LBA1; J Clin Oncol 2022;40:2878-2888]

Among 31 patients with unre­sectable liver‑only disease, the objec­tive response rate (ORR) in the liver reached 71 percent, with complete and partial response rates of 6.5 and 64.5 percent, respectively. [Front Oncol 2023;13:1138357] Secondary liver treat­ment was undertaken in 51.6 percent of these patients, and the R0 resection (ie, no microscopic or macroscopic residual tumour) rate was 32.3 percent, closely mirroring R0 resection rates reported in previous intensive conversion–focused studies. [Front Oncol 2023;13:1138357; Lancet Oncol 2010;11:38-47; J Clin Oncol 2022;40:2878-2888]

The mCAPIRI‑P regimen was as­sociated with an acceptable toxicity profile. Grade 3/4 toxicities occurred in 43.4 percent of patients, driven mainly by uncomplicated neutropenia (32.1 percent), uncomplicated leukopenia (16 percent), and diarrhoea (11.3 percent), while febrile neutropenia was observed in 3.8 percent. Dose reductions to <70 percent of the intended dose of capecit­abine, irinotecan and panitumumab were required in 9.4, 5.7 and 3.8 per­cent of patients, respectively, while 4.7 percent discontinued treatment due to toxicity. These data indicate that, with appropriate dose tailoring and sup­portive care, a 3‑weekly mCAPIRI‑P regimen is both feasible and safe as a first-line regimen for patients with RAS wild-type advanced CRC. [Front Oncol 2023;13:1138357]

Although not designed to compare biologics, the cohort’s high ORR (71 percent) and substantial R0 resection rate (32.3 percent) in liver‑only disease resonate with findings of the multicentre retrospective study in Taiwan, highlight­ing panitumumab’s role in facilitating curative‑intent resection in patients with RAS wild‑type mCRC. [Front Oncol 2023;13:1138357; Chang PH, et al, ESMO Asia 2025, abstract 235eP]

Conclusions
In patients with RAS wild‑type mCRC in whom conversion resection of hepatic or lung metastases is a major therapeutic objective, data from the ret­rospective study in Taiwan as well as earlier real-world data support first-line use of panitumumab‑based regimens. While OS results are comparable between panitumumab-and cetuximab-containing regimens, higher resection rates associated with panitumum­ab suggest that it may better align with a curative‑intent strategy with­out sacrificing long‑term survival in suitable candidates.

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