Volker Heinemann, MD, PhD, director of the Comprehensive Cancer Center at Ludwig Maximilian University of Munich, compares the use of depth of response and RECIST criteria to measure responses in patients with colorectal cancer (CRC).

The general goal, says Heinemann, is to find a surrogate parameter that can be measured early on and which relates a patient's response to overall survival. Through the use of depth of response, oncologists can, in fact, find early tumor shrinkage in patients with CRC, and relate that to prolonged survival.

Depth of response goes one step beyond the RECIST criteria, according to Heinemann. RECIST differentiates responses with categories like partial and complete responses, whereas depth of response is a continuous parameter. Therefore, says Heinemann, depth of response allows oncologists to more precisely demonstrate how effective a treatment was for a particular patient.

Videos

Volker Heinemann, MD, PhD, director of the Comprehensive Cancer Center at Ludwig Maximilian University of Munich, compares the use of depth of response and RECIST criteria to measure responses in patients with colorectal cancer.

Dr. Heinemann on the Use of Depth of Response and RECIST in CRC

Volker Heinemann, MD, PhD, director of the Comprehensive Cancer Center at Ludwig Maximilian University of Munich, discusses the broad clinical implications of the SIRFLOX findings for patients with metastatic colorectal cancer (mCRC).

The SIRFLOX trial demonstrated that the addition of selective internal radiation therapy with SIR-Spheres Y-90 resin microspheres to standard first-line chemotherapy significantly increased hepatic depth of response in patients with mCRC, Heinemann explains. He adds that, because of these results, if a major improvement in progression-free survival (PFS) in a vital organ such as the liver is observed, researchers can conclude that there is a high probability that this will translate to prolonged overall survival (OS).

Comparable data from the CLOCK study explored chemotherapy versus chemotherapy plus radio frequency ablation which, he adds, can be interpreted as treatment intensification with regard to liver metastases. Investigators were able to demonstrate that PFS could be markedly improved in the liver and that this was also associated with improved OS.

Dr. Heinemann on Implications of SIRFLOX Study for mCRC

Volker Heinemann, MD, PhD, director of the Comprehensive Cancer Center at Ludwig Maximilian University of Munich, discusses using depth of response as an appropriate endpoint in studies examining patients with metastatic colorectal cancer (mCRC).

Depth of response is an important endpoint to measure when investigating triplet chemotherapy regimens, such as FOLFOXIRI, or the addition of an 

-targeted agent to a doublet-chemotherapy regimen in 

It is here that depth of response, as well as tumor shrinkage, can be associated with overall survival, Heinmann says.

Dr. Heinemann on Using Depth of Response in Pretreated Patients With CRC

Volker Heinemann, MD, PhD, director of the Comprehensive Cancer Center at Ludwig Maximilian University of Munich, discusses surrogate markers aside from progression-free survival (PFS) in studying patients with colorectal cancer (CRC).

Until recently, PFS has been the most popular surrogate endpoint predictive of survival and has also been used in registration trials, Heinemann says. With the addition of targeted therapies to the landscape of CRC, it was found that PFS was losing its predictive power as a marker, he explains.

PFS is no longer a very approrpriate marker to use for overall survival. However, other and perhaps better endpoints to use, he adds, include first-line treatment response rate, depth of response, and tumor shrinkage.

Dr. Heinemann on Surrogate Markers Beyond PFS in Patients With CRC

Volker Heinemann, MD, PhD, a professor of medical oncology at the University of Munich in Munich, Germany, discusses results from the phase III FIRE-3 trial that looked at FOLFIRI plus bevacizumab or cetuximab as a first-line treatment for patients with wild-type KRAS metastatic colorectal cancer.

In the trial, the objective response rate (ORR) was comparable between the two treatments (bevacizumab and cetuximab). However, in patients who received at least 3 cycles of treatment and had one imaging procedure after baseline, a 10% ORR benefit was observed in the cetuximab arm, Heinemann notes.

View more from the 2013 ASCO Annual Meeting

Volker Heinemann, MD, PhD, from the University of Munich, discusses results from the phase III FIRE-3 trial that looked at FOLFIRI plus bevacizumab or cetuximab as a first-line treatment for patients with wild-type KRAS metastatic colorectal cancer.

Volker Heinemann, MD, PhD

Articles

Dr. Heinemann on the Use of Depth of Response and RECIST in CRC

Dr. Heinemann on Implications of SIRFLOX Study for mCRC

Dr. Heinemann on Using Depth of Response in Pretreated Patients With CRC

Dr. Heinemann on Surrogate Markers Beyond PFS in Patients With CRC

Dr. Heinemann Reviews the FIRE-3 Trial Results