Bevacizumab (Bev) with or without erlotinib as maintenance therapy, following induction first-line chemotherapy plus Bev, in patients (pts) with metastatic colorectal cancer (mCRC): Efficacy and safety results of the International GERCOR DREAM phase III trial.

Abstract

LBA3500^ Background: Therapy targeting VEGF or EGFR demonstrated clinical activity in combination with chemotherapy (CT) in mCRC but monoclonal antibodies cannot be associated. The DREAM trial compares a maintenance therapy (MT) with bev +/- EGFR tyrosine kinase inhibitor erlotinib (E) after a first-line Bev-based induction therapy (IT) in pts with mCRC. Methods: Pts with previously untreated and unresectable mCRC were eligible. After a Bev-based IT with FOLFOX or XELOX or FOLFIRI, pts without disease progression were randomized to MT between Bev alone (Bev 7.5 mg/kg q3w; arm A) or Bev+E (B 7.5 mg/kg q3w, E 150 mg/day continuously; arm B). Pts were treated until progression or unacceptable toxicity. The primary endpoint was PFS on MT. Results: The study enrolled 700 pts from 01/2007 to 11/2011 in 3 countries (France, Canada, Austria). 446 (63.7%) pts were randomized for MT (arm A, N=224; arm B, N=222). Among the 446 randomized pts, IT regimen was FOLFOX-Bev in 265 pts (59.4%), XELOX-Bev in 135 pts (30.3%), and FOLFIRI-Bev in 46 pts (10.3%). Baseline characteristics of randomized pts were (arm A/B): ECOG PS 0, 60% in both arms; normal LDH level 47%/49%; normal alkaline phosphatase level 48%/50%; synchronous metastasis 83%/82%. The median no of MT cycles was 6 in both arms. With a median follow-up of 31.0 months, 327 PFS events were observed. Median MT-PFS were 4.6 m in arm A vs 5.8 m in arm B (HR 0.73 [95%CI: 0.59-0.91], P=.005). Median PFS from inclusion were 9.2 m vs 10.2 m. During MT, in arm A vs arm B, grade 3-4 diarrhea (<1% vs 9%) and grade 3 skin toxicity (0% vs 19%) were the main differences in toxicity. Severe adverse events from randomization related to B or E were 6 in arm A and 7 in arm B. Overall survival is not mature. Conclusions: The addition of erlotinib to bevacizumab after induction therapy significantly improves the duration of maintenance PFS, following induction with first-line chemotherapy plus bevacizumab, in patients with unresectable metastatic colorectal cancer.

Intermittent versus continuous erlotinib with concomitant modified “XELOX” (q3W) in first‐line treatment of metastatic colorectal cancer

“…The development of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR TKI) in the treatment of metastatic colorectal cancer (mCRC) has taken a new turn with the recent reports on the DREAM and the DUX studies, which showed that erlotinib may play a role when combined with either bevacizumab or cetuximab in the palliative treatment of mCRC. Studies in preclinical models of CRC have demonstrated an additive to synergistic effect on growth inhibition when an EGFR TKI is combined with chemotherapy .…”

The combination of systemic chemotherapy and local treatment may improve the survival of patients with unresectable metastatic colorectal cancer

“…A number of clinical studies (18,19) support the use of capecitabine as maintenance therapy, as it has been shown to prolong PFS, but provides no OS benefit. It is recommended that such patients receive a local, minimally invasive treatment to achieve TFS.…”

Preoperative Radiation Therapy With Concurrent Capecitabine, Bevacizumab, and Erlotinib for Rectal Cancer: A Phase 1 Trial

“…The much higher pathologic response rate seen in this trial suggests that dual targeting of the VEGF and EGFR pathways may have a synergistic effect on chemoradiation. There is prior evidence supporting the combination of bevacizumab and erlotinib in colorectal cancer; a randomized trial has shown that maintenance therapy with bevacizumab and erlotinib improves progression-free survival, compared to maintenance therapy with bevacizumab alone in patients with metastatic colorectal cancer 24 . The role of erlotinib appeared to be independent of KRAS status in that trial 25 .…”