A phase 2 clinical trial conducted in Japan has demonstrated that the combination of bevacizumab (Avastin) and capecitabine (Xeloda) provides significant clinical benefit for elderly patients with metastatic colorectal cancer (mCRC) who are ineligible for more intensive chemotherapy regimens.
The study (UMIN000005209), published in the journal In Vivo, evaluated this combination in patients who were either 76 years or older, or between 65-75 years of age but unsuitable for oxaliplatin- or irinotecan-based regimens. The results showed a median progression-free survival (PFS) of 10.3 months (95% CI, 9.2-15.4), with impressive 6-month and 12-month PFS rates of 87.5% and 35.8%, respectively.
"This study represents the first phase 2 trial assessing the efficacy of first-line capecitabine plus bevacizumab in Japanese patients with mCRC ineligible for intensive chemotherapy," the study authors noted. "The study met its primary end point [of PFS]. These results underscore the safety and efficacy of first-line capecitabine in combination with bevacizumab as a viable therapeutic option for vulnerable elderly Japanese patients."
Study Design and Patient Population
The trial enrolled 33 patients with histologically or cytologically confirmed colon or rectal carcinomas. Eligible participants had evaluable disease per RECIST 1.1 criteria, creatinine clearance of at least 30 mL per minute, adequate organ function, a life expectancy of 8 weeks or longer, and an ECOG performance score of 0 to 2.
Patients received capecitabine at 2000 mg/m² per day for 14 days along with bevacizumab at 7.5 mg/kg on day 1 of each 3-week cycle. Treatment continued until disease progression, intolerable adverse effects, or withdrawal of consent. The protocol allowed for dose modifications of capecitabine based on renal function or toxicities.
The median age of participants was 78 years (range, 67-86), with 75.8% of patients being at least 76 years old. The study population was balanced by gender (51.5% male), and most patients had an ECOG performance status of 0 or 1 (84.8%). Tumor locations were primarily in the colon (60.6%) with the remainder in the rectum (39.4%).
Efficacy Outcomes
The combination therapy demonstrated notable antitumor activity with an overall response rate (ORR) of 30.3% (95% CI, 15.6%-48.7%), with all responses being partial. Additionally, 60.6% of patients achieved stable disease, resulting in a disease control rate of 91.0% (95% CI, 75.7%-98.1%).
Survival outcomes were also encouraging, with a median overall survival (OS) of 27.9 months (95% CI, 24.2-50.1). The 12-month and 24-month OS rates were 93.8% and 68.1%, respectively. The median time to treatment failure was 9.2 months (95% CI, 6.9-11.5).
"Our data demonstrate the good antitumor activity of capecitabine plus bevacizumab as a first-line treatment for patients with mCRC, achieving an overall response rate of 30.3%, which is comparable [with] or even higher than that previously reported in clinical trials," the investigators reported.
Safety Profile
The regimen demonstrated a manageable safety profile appropriate for an elderly population. The most common grade 3/4 non-hematological toxicities were hypertension (36.0%) and hand-foot syndrome (12.0%). One patient experienced grade 4 gastrointestinal perforation, and two patients developed grade 3 proteinuria. Severe hematological toxicities were rare, with only one patient each experiencing grade 3 neutropenia and anemia.
Treatment discontinuations due to treatment-related adverse events occurred in 15.2% of patients. No treatment-related deaths were observed during the study.
Building on Previous Evidence
The current findings build upon the phase 3 AVEX trial (NCT00484939), which previously demonstrated that first-line capecitabine plus bevacizumab was effective and well tolerated in a global population of patients 70 years of age or older with mCRC. In that study, the combination significantly improved median PFS compared to capecitabine alone (9.1 months vs. 5.1 months; HR, 0.53; P < .0001).
The Japanese investigators sought to confirm these benefits specifically in their patient population, and the results appear consistent with or even slightly better than those observed in the global AVEX trial.
Clinical Implications
The study authors emphasized the advantages of this combination regimen for elderly patients: "The advantage of the capecitabine plus bevacizumab regimen is that it allows for treatment with fewer toxicities, such as peripheral neuropathy or severe bone marrow suppression, [and maintains] the quality of life during treatment."
Nearly half (48.5%) of the patients went on to receive subsequent therapies after progression, including oxaliplatin-containing regimens (21.2%), irinotecan alone or with bevacizumab (12.1%), and anti-EGFR antibody–containing regimens (9.1%).
These findings provide important evidence for oncologists treating elderly patients with mCRC who may not be candidates for more intensive chemotherapy regimens. The combination of bevacizumab and capecitabine offers an effective and well-tolerated option that can provide meaningful clinical benefit while preserving quality of life in this vulnerable population.
