Tanios Bekaii-Saab, MD: Considering a Second EGFR-directed Therapy

Would you consider a second EGFR-directed therapy?

Dr. Bekaii-Saab looks at the data available and suggests that when one moves from a VEGF-directed therapy in the first-line, it is still possible to continue through a VEGF-directed therapy in the second-line. And this patient who received bevacizumab in the first-line, it is justifiable to continue with the bevacizumab and just switch the chemotherapy backbone rather than to include an anti-EGFR therapy through this line.

It is equally reasonable to consider an EGFR directed therapy. Most oncologists would continue with a VEGF directed-therapy. And more specifically with the bevacizumab and the main reason for that is you figure that the toxicities, you figure that essentially how well the patients are going to go through it, and it’s just a lot of familiarity with the bevacizumab, it makes it easy just to continue through and now we have data that supports its continuation from first- to second-line.

There are certain instances where it would make more sense to switch to an EGFR inhibitor. Patient becomes more symptomatic and you need a response. Continuing VEGF inhibition beyond first-line does not increase the response rate and EGFR inhibitors do. So if one requires a response, then it’s preferable to do an EGFR inhibitor. And if there were any complications with VEGF inhibitors, or contraindication to VEGF inhibitors, then you would do the same.

And then there are different practices. Dr. Bekaii-Saab's practice actually starts with a little bit different backbone to start with, FOLFIRI rather than FOLFOX with bevacizumab and in patients like that he would actually continue the same chemotherapy backbone. So there are different permutations of how one can do that. It’s acceptable to include an EGFR inhibitor in this setting. With this and with the data that we have about VEGF inhibitors, it’s probably just easier to go from first- to second-line with a VEGF inhibitor, and continue the bevacizumab through and delay EGFR inhibitors to third-line.

CASE 1: Metastatic Colorectal Cancer (CRC)

Neil H. is a 62-year-old construction manager from Houston, Texas.

• His prior medical history is notable for obesity, mild hypertension, hyperuricemia, and gout

The patient was diagnosed with colon cancer in February 2011, after reporting to his PCP with symptoms of intermittent nausea, vomiting, and blood in his stool

• Patient underwent resection of the sigmoid colon with lymph node evaluation (12 nodes examined), which showed adenocarcinoma stage T3N0M0; mutational status showed RAS WT; BRAF negative

In January of 2013, he presented to his oncologist for evaluation after his CEA had increased to 85 ng/mL.

The patient was asymptomatic at the time of recurrence

CT scan showed multiple unresectable metastatic lesions to the liver and lung; the patient’s ECOG performance status was 0

He received initial therapy with FOLFOX and bevacizumab for metastatic disease

After 6 cycles the patient experienced a good response but developed grade 3 neuropathy and oxaliplatin was discontinued

The patient was continued on 5FU with bevacizumab with eventual improvement of his neuropathy symptoms; his disease continued to be stable

In February of 2015, the patient presents with fatigue, nonexertional dyspnea, and cough, and his CEA had increased to 110 ng/mL.

• CT scan was consistent with progression of liver and pulmonary lesions