Neoadjuvant Bevacizumab, Capecitabine and Radiation Therapy With or Without Oxaliplatin Locally Advanced Rectal Cancer

Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.

Time frame: 4 months

Population: Patients who had undertaken surgery and had pathology materials available for central review (centrally reviewed subset)

Baseline tumour measurements were performed within 4 weeks prior to treatment start (RECIST). The same methods of assessment (CT and/or MRI) were used for each measurable lesion at baseline and during follow-up. * Complete Response (CR) is disappearance of all clinical and radiological evidence of tumour (both target and non-target lesions). * Partial Response (PR) is at least a 30% decrease in the sum of LD of target lesions, taking as reference the baseline sum of tumour longest diameters (LD). * Stable Disease (SD) is steady state of disease. Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD. * Progressive Disease (PD) is at least a 20% increase in the sum of LD of measured lesions taking as references the smallest sum LD recorded since the treatment started. Appearance of new lesions constitutes PD. In exceptional circumstances, unequivocal progression of non-target lesions was considered evidence of PD.

Time frame: 3 months

Population: Intent to treat, all registered patients

Counts and proportions of patients deceased (post-study).

Time frame: up to 5 years

Population: Intent to treat in follow up (one patient in Arm 1 lost to follow up).

Histopathologic R0 resection rate was defined as margins histologically negative for tumour involvement after resection. The circumferential resection margin (CRM) is considered to be involved if microscopic tumour is present \<1mm from or at the inked circumferential or radial resection margin. Data on quality of mesorectal excision were expected but not collected consistently.

Time frame: 4 months

Population: Patient in Arm 2 that discontinued chemoradiotherapy due to major toxicity and had surgery off protocol is counted here as well

Dworak tumour regression grades (TRG) were used to assess pathologic response: TRG0=no regression. TRG1=dominant tumor mass with obvious fibrosis and/or vasculopathy; TRG2=dominant fibrotic changes with few tumour cells or groups; TRG3=very few (difficult to find microscopically) tumour cells in fibrotic tissue with or without mucus substance. TRG4=no intact viable tumour cells, only fibrotic mass or presence of mucin lakes without associated malignant cells (total tumour regression). Pathologic assessments of tumour response post chemoradiotherapy as provided by investigators (read by local pathologists on operative specimens) were reviewed centrally for all pts for whom surgical materials were available (centrally reviewed set). The diagnosis of independent central reviewers primed. Pathologic complete response rates (TRG4) are reported (%). Good (TRG3 and TRG4 together) and little (TRG 0,1 and 2) tumour regression rates are summarized. For these 2 last rows, % add to 100.

Time frame: 4 months

Population: Centrally reviewed subset

Counts and proportions of patients experiencing recurrence of disease (local and distant).

Time frame: up to 5 years

Population: Intent to treat (one patient lost to follow-up)

Adverse events graded as per NCI CTCAE (US National Cancer Institute Common Terminology Criteria for Adverse Events) version 3.0. All Serious Adverse Events occurrences are reported and counts are summarized here; all Adverse Events (all grades) related and not related to study treatment are reported and summarized here; all severe laboratory events (hematology and biochemistry Gr 3 and higher) are reported and summarized here; all severe postoperative complications (Gr 3 and higher) occurred within the first month post surgery are reported and summarized here. See section Adverse events for details.

Time frame: continuous up to 1 year

Population: Intent to treat