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Antibody Selection and Tumor Sidedness in CRC

Insights From: Andrea Cercek, MD, Memorial Sloan Kettering Cancer Center; Tanios Bekaii-Saab, MD, Mayo Clinic
Published: Wednesday, Feb 07, 2018



Transcript: 

Tanios Bekaii-Saab, MD: Over the last few years, we’ve understood the importance of right- versus left-sided tumors in the more advanced setting. We’ve understood the importance of choice of biologics, at least on the right side versus the left side. If we had to choose a biologic on the right side, bevacizumab seems to add value, or add improvement, in outcomes. EGFR inhibitors unfortunately do not.

On the left side, there may be a slight edge for an EGFR inhibitor. But overall, when we take in all considerations, it’s likely that patients will benefit from either bevacizumab or cetuximab. The discussion will certainly have to include both agents: the EGFR inhibitor and bevacizumab, cetuximab, or panitumumab versus bevacizumab, given the data from CALGB 80405 and CALGB 804053. In the United States, most of our patients and most of our physicians still favor bevacizumab in the first line on the left side.

Interestingly, one paper in ASCO GI that was presented looked at 2 large phase III randomized studies looking at 1590 patients. What this paper suggested is that patients, whether on the right side or the left side, still benefit from the addition of bevacizumab to chemotherapy versus no bevacizumab. Now, why is this important? Because when we look at CALGB 80405 and CALGB 804053, we don’t have a chemotherapy-alone arm. What we have is chemotherapy plus bevacizumab versus chemotherapy plus cetuximab. So, we don’t have a clean no-chemotherapy arm to help us understand if on the right side, where patients do extremely bad or relatively bad, do they really benefit from the addition of bevacizumab to chemotherapy.

The cumulative understanding from those 2 studies is that whether your tumor’s on the right side or the left side, when you add bevacizumab to chemotherapy you do much better than on chemotherapy alone. So, bevacizumab’s activity seems to be independent of tumor location. Right or left, bevacizumab plus chemotherapy seems to improve outcome.

Andrea Cercek, MD: Sidedness has been a hot topic in GI oncology, left versus right, with regard to outcomes. We learned, over the last several years, that patients with right-sided tumors do not do as well as patients with left-sided tumors and, importantly, that they don’t respond to anti-EGFR therapy. This was in the metastatic setting.

Today, the data at ASCO demonstrated with an analysis of the SCOT study, which looked at adjuvant chemotherapy in resected stage 2 or 3 colon cancer, that, in fact, patients with right-sided tumors had a worse rate of disease-free survival than patients with left-side tumors. This did not appear to be influenced by chemotherapy, but rather it was likely biology that was contributing to this because they developed earlier recurrences than the patients with left-sided tumors. This really pointed to the fact that it’s the biology that is driving this difference.

Transcript Edited for Clarity 
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Transcript: 

Tanios Bekaii-Saab, MD: Over the last few years, we’ve understood the importance of right- versus left-sided tumors in the more advanced setting. We’ve understood the importance of choice of biologics, at least on the right side versus the left side. If we had to choose a biologic on the right side, bevacizumab seems to add value, or add improvement, in outcomes. EGFR inhibitors unfortunately do not.

On the left side, there may be a slight edge for an EGFR inhibitor. But overall, when we take in all considerations, it’s likely that patients will benefit from either bevacizumab or cetuximab. The discussion will certainly have to include both agents: the EGFR inhibitor and bevacizumab, cetuximab, or panitumumab versus bevacizumab, given the data from CALGB 80405 and CALGB 804053. In the United States, most of our patients and most of our physicians still favor bevacizumab in the first line on the left side.

Interestingly, one paper in ASCO GI that was presented looked at 2 large phase III randomized studies looking at 1590 patients. What this paper suggested is that patients, whether on the right side or the left side, still benefit from the addition of bevacizumab to chemotherapy versus no bevacizumab. Now, why is this important? Because when we look at CALGB 80405 and CALGB 804053, we don’t have a chemotherapy-alone arm. What we have is chemotherapy plus bevacizumab versus chemotherapy plus cetuximab. So, we don’t have a clean no-chemotherapy arm to help us understand if on the right side, where patients do extremely bad or relatively bad, do they really benefit from the addition of bevacizumab to chemotherapy.

The cumulative understanding from those 2 studies is that whether your tumor’s on the right side or the left side, when you add bevacizumab to chemotherapy you do much better than on chemotherapy alone. So, bevacizumab’s activity seems to be independent of tumor location. Right or left, bevacizumab plus chemotherapy seems to improve outcome.

Andrea Cercek, MD: Sidedness has been a hot topic in GI oncology, left versus right, with regard to outcomes. We learned, over the last several years, that patients with right-sided tumors do not do as well as patients with left-sided tumors and, importantly, that they don’t respond to anti-EGFR therapy. This was in the metastatic setting.

Today, the data at ASCO demonstrated with an analysis of the SCOT study, which looked at adjuvant chemotherapy in resected stage 2 or 3 colon cancer, that, in fact, patients with right-sided tumors had a worse rate of disease-free survival than patients with left-side tumors. This did not appear to be influenced by chemotherapy, but rather it was likely biology that was contributing to this because they developed earlier recurrences than the patients with left-sided tumors. This really pointed to the fact that it’s the biology that is driving this difference.

Transcript Edited for Clarity 
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