番茄社区

CHICAGO -- In carefully selected patients diagnosed with metastatic colorectal cancer receiving standard first-line chemotherapy, treatment with the EGFR inhibitor panitumumab (Vectibix) significantly extended survival compared with bevacizumab, a researcher reported here.

For patients with RAS wild-type histology and left-sided cancers in the PARADIGM study, those treated with panitumumab had a median overall survival (OS) of 37.9 months, as compared with 34.3 months those who received the VEGF inhibitor bevacizumab, a relative risk reduction of 18% (P=0.031), said Takayuki Yoshino, MD, PhD, of National Cancer Center Hospital East in Kashiwa, Japan, in a plenary presentation at the (ASCO) annual meeting.

"Panitumumab plus modified FOLFOX6 therapy demonstrated the longest survival ever reported in the first-line treatment for unresectable metastatic colorectal cancer in phase III trial," Yoshino said. "These results have established a standard first-line combination regimen for patients with RAS wild-type left-sided metastatic colorectal cancer."

As this primary endpoint was positive, the researchers then analyzed the entire patient population, without regard to cancer location. Median OS here also significantly favored panitumumab (36.2 vs 31.3 months, respectively, P=0.030), though the OS difference for right-sided tumors, specifically, was not significantly different between groups, Yoshino reported.

"We are constantly looking for new breakthroughs, and this is one of the longest overall survivals ever reported," ASCO expert Cathy Eng, MD, of Vanderbilt-Ingram Cancer Center in Nashville, Tennessee, told 番茄社区. "We have not had a prospective trial that specifically looks at left-sided colorectal cancer, so this study adds quite a bit to the literature, and I think we are quite excited about the possibilities of increasing the survival of our patients.

Eng called the added months of survival "clinically meaningful."

"This is the first study to prospectively validate the use of anti-EGFR treatment in left-sided colorectal tumors," she said. "Treatment did allow some of these unresectable patients to eventually undergo curative surgery. This is a win for a highly selected group of patients with left-sided metastatic tumors. This PARADIGM study will change clinical practice."

Colorectal cancer is the third most diagnosed cancer worldwide, and an estimated 1.9 million new cases were diagnosed in 2020, with over a third of cases metastatic at diagnosis, Yoshino noted.

"There has been retrospective evidence showing a longer overall survival with anti-EGFR antibody over anti-VEGF antibody in patients with RAS wild-type metastatic colorectal cancer and left-sided primary tumors -- about 35% of metastatic colorectal cancers," he said. "Nevertheless, both anti-EGFR and anti-VEGF are used in patients with RAS wild-type and left-sided metastatic colorectal cancer, which warrant prospective comparison in this refined population."

In the phase III, open-label, multicenter trial, 823 patients diagnosed with metastatic colorectal cancer (73% of which were left-sided tumors) and harboring RAS wild-type tumors were assigned 1:1 to receive chemotherapy plus either panitumumab or bevacizumab. Patients had to present with unresectable disease and to have received no prior chemotherapy. Treatment in both arms continued until disease progression, intolerable toxicity, curative resection, or withdrawal from the study.

Progression-free survival was 13.7 months among the patients in the panitumumab group and 13.2 months in the bevacizumab cohort, a non-significant difference, said Yoshino. The response rate and the curative resection rate -- an indication that no tumor remains in the body -- were both higher with panitumumab compared with bevacizumab.

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