Paul E. Oberstein, MD, associate professor, Department of Medicine, director, Gastrointestinal Medical Oncology Program, assistant director, Pancreatic Cancer Center, NYU Grossman School of Medicine, NYU Langone Health’s Perlmutter Cancer Center, discusses remaining challenges in metastatic colorectal cancer (CRC).

Although targeted therapies and immunotherapy have shown favorable results, they have only been beneficial for a minority of patients, Oberstein says. Therefore, it is important to find more treatment approaches that are effective for a wider subset of patients, Oberstein explains.

Moreover, although the incidence of CRC has gone down among the overall population, the incidence of CRC is rising among adults under the age of 50 years in the United States, Oberstein continues. It is important to understand more about why this has happened, as well as how to target those patients, Oberstein says.

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Paul E. Oberstein, MD, discusses remaining challenges in metastatic colorectal cancer.


Dr. Oberstein on Remaining Challenges in Metastatic CRC

Paul E. Oberstein, MD, associate professor, Department of Medicine, director, Gastrointestinal Medical Oncology Program, assistant director, Pancreatic Cancer Center, NYU Grossman School of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the phase 2/3 CheckMate 9X8 trial (NCT03414983) in metastatic colorectal cancer (CRC).

CheckMate 9X8 evaluated standard-of-care chemotherapy plus bevacizumab (Avastin) with or without nivolumab (Opdivo) in the first-line treatment of patients with metastatic CRC.

The primary end point of the trial evaluated progression-free survival (PFS), and data did not show that there was a PFS benefit when adding nivolumab to standard-of-care chemotherapy, Oberstein says. The median PFS was identical in both groups, Oberstein explains.

Despite being a negative study due to the primary end point not being met, the 2-year overall survival data benefited the group that received nivolumab, Oberstein continued. Further research is needed to properly identify patients who could benefit from the addition of nivolumab to chemotherapy, Oberstein concludes.

Paul E. Oberstein, MD, discusses the phase 2/3 CheckMate 9X8 trial in metastatic colorectal cancer.


Dr. Oberstein on the CheckMate 9X8 Trial in Metastatic CRC

Paul E. Oberstein, MD, associate professor, Department of Medicine, director, Gastrointestinal Medical Oncology Program, assistant director, Pancreatic Cancer Center, NYU Grossman School of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the utilization of ctDNA in metastatic colorectal cancer (CRC).

By helping detect the burden of disease, ctDNA can provide insight to how much chemotherapy a patient needs, as well as their risk of recurrence, Oberstein says. While ctDNA has shown the ability to predict risk of recurrence, it is still unknown if it can predict how a patient will respond to chemotherapy or what the best agent would be to combine with chemotherapy, Oberstein explains.

These answers can only be obtained through clinical trials, and there are multiple trials in progress aiming to find how to use information from ctDNA to decide whether to escalate or deescalate therapy, Oberstein concludes.

Paul E. Oberstein, MD, discusses the utilization of ctDNA in metastatic colorectal cancer.


Dr. Oberstein on the Utilization of CtDNA in Metastatic CRC

Paul E. Oberstein, MD, associate professor, Department of Medicine, director, Gastrointestinal Medical Oncology Program, assistant director, Pancreatic Cancer Center, NYU Grossman School of Medicine, Perlmutter Cancer Center, NYU Langone Health, discusses the current treatment landscape of colorectal cancer (CRC).

For the majority of patients with CRC, multi-agent chemotherapy is administered in both the first- and second-line settings, Oberstein says. Depending on a patient’s mutational status, targeted agents could also be deployed in these settings, Oberstein says.

For patients who progress to the third line, single-agent regorafenib (Stivarga) and TAS-102 (trifluridine/tipiracil; Lonsurf) have demonstrated efficacy in randomized trials, Oberstein explains. However, there is no standard of care beyond the third line, and enrollment on clinical trials are highly encouraged, Oberstein adds.

More patients with CRC are being classified into subsets based on genetic markers, and these subsets can receive tailored therapy in earlier settings, Oberstein continues. The increase in biomarkers has allowed for more patients with mutations to be identified, and clinical trials plus more standardized testing have changed how treatment is tailored, Oberstein concludes.

Paul E. Oberstein, MD, discusses the current treatment landscape of colorectal cancer.


Dr. Oberstein on the Current Treatment Landscape of CRC

Paul E. Oberstein, MD, assistant professor of medicine, assistant director, Pancreatic Cancer Center, director, Gastrointestinal Medical Oncology Program, NYU Langone’s Perlmutter Cancer Center, discusses the use of pegylated hyaluronidase (PEGPH20) in advanced pancreatic cancer.

PEGPH20, is an investigational agent and potential therapy for patients with advanced pancreatic cancer, says Oberstein. The mechanism of that agent breaks down hyaluronan, or hyaluronic acid, in the tumor environment. This potentially opens the tumor up to receive more chemotherapy or maybe even be able to target tumors directly.

A large phase II clinical trial showed some benefit of PEGPH20 in combination with gemcitabine and nab-paclitaxel (Abraxane). However, another trial showed no benefit of PEGPH20 in combination with an alternative chemotherapy backbone, modified FOLFIRINOX. Oberstein says that physicians need to better understand exactly who and when patients will benefit from the agent. This underscores the need for more clinical trials, observes Oberstein.

Paul E. Oberstein, MD, assistant professor of medicine, assistant director, Pancreatic Cancer Center, director, Gastrointestinal Medical Oncology Program, NYU Langone’s Perlmutter Cancer Center, discusses the use of PEGPH20 in advanced pancreatic cancer.

Paul E. Oberstein, MD

Articles

Dr. Oberstein on Remaining Challenges in Metastatic CRC

Dr. Oberstein on the CheckMate 9X8 Trial in Metastatic CRC

Dr. Oberstein on the Utilization of CtDNA in Metastatic CRC

Dr. Oberstein on the Current Treatment Landscape of CRC

Dr. Oberstein on PEGPH20 in Patients With Pancreatic Cancer