Byrne Lee, MD
In past years, management of metastatic colorectal cancer (mCRC) has required a more palliative approach, but recent therapeutic advances have improved patient outcomes. Despite this progress, there is still much work left to be done, said Byrne Lee, MD.
Investigators had hoped that data from recent studies evaluating the use of hyperthemic intraperitoneal chemotherapy (HIPEC)—particularly PRODIGE 7 and COLOPEC—would help lead to a more refined treatment approach for patients with peritoneal metastases. However, both trials failed to demonstrate the benefit of HIPEC in this patient subset.
In PRODIGE 7, patients were randomized to receive an addition of HIPEC oxaliplatin heated to 43 degrees Celsius in an attempt to increase efficacy, said Lee, who is the chief of the Upper GI and Mixed Tumor Surgery Service and an associate professor of surgical oncology at City of Hope. Investigators found that there was no survival benefit to heated chemotherapy delivered straight to the abdomen in patients with peritoneal metastasis. Median overall survival in the non–HIPEC arm was 41.2 months compared with 41.7 months for the patients treated with HIPEC.1
Relapse-free survival was 11.1 months for patients treated without HIPEC versus 13.1 months for those treated with heated chemotherapy.
The COLOPEC study, results of which were presented at the 2019 Gastrointestinal Cancers Symposium, showed benefit for surgical debulking, but did not succeed in bolstering the need for HIPEC in these patients. Regarding the primary endpoint of 18-month peritoneal metastasis-free survival rate, researchers observed no statistically significant difference: 76% for patients in the control arm versus 81% for patients treated with surgery followed by HIPEC (HR, 0.86; 95% CI, 0.51-1.54).2
Although some of these patients may benefit from this modality, Lee said that more evidence is needed before this approach can become standard practice. He added that this is not the only regional therapy under investigation for patients with peritoneal metastasis. A newer delivery treatment, referred to as pressurized intraperitoneal aerosol chemotherapy (PIPAC), is of interest and is already being used in Europe and Asia.
In an interview with OncLive
at the 2019 State of the Science Summit™ on Gastrointestinal Cancers, Lee further discussed regional treatment strategies for patients with mCRC.
OncLive: What is the use of intraperitoneal chemotherapy and surgery for the treatment of peritoneal metastases for CRC?
: In the past, this has been a deadly disease with a very poor prognosis. Over the years, however, we have been utilizing aggressive cytoreductive and debulking surgeries to rid the peritoneum of disease. We have also included intraperitoneal chemotherapies, which have been shown to improve survival in recent randomized trials. I shared some of the updates that were presented at the 2019 Gastrointestinal Cancers Symposium. There does appear to be an improvement with cytoreductive surgery, but the use of intraperitoneal chemotherapy may or may not improve survival. We definitely need more studies to improve our knowledge on this.
Could you elaborate on some of these studies that were presented at the 2019 Gastrointestinal Cancers Symposium?
There was a study presented in 2018 by a large French group, the long-awaited PRODIGE 7 trial, which looked at the use of cytoreductive surgery with or without HIPEC for the treatment of CRC with peritoneal metastasis. In this trial, patients were randomized to receive either surgery or surgery with HIPEC; this utilized a more European regimen comprised of oxaliplatin perfused for 30 minutes at 43 degrees Celsius. In that trial, there was no improvement in overall survival or progression-free survival (PFS) when HIPEC was used. It did, however, show that cytoreductive surgery works—there was a median PFS of approximately 40 months in both arms, and we have used this study to show that aggressive surgical debulking can help certain patients with peritoneal metastasis.