Sequencing, Patient Selection Among Challenges in GI Cancers

Brian Hemphill, MD

The excitement surrounding immunotherapy is palpable in gastrointestinal (GI) cancers; however, the treatment only develops responses in a minority of patients, studies have shown.

Therefore, explains Brian Hemphill, MD, the future treatment landscape in these areas will likely include combination regimens and decision-making based on patient molecular profiles.

For example, an ongoing phase Ib/II clinical is investigating the clinical activity and safety of the combination of the PD-1 inhibitor pembrolizumab (Keytruda), trastuzumab (Herceptin), capecitabine, and cisplatin in patients with HER2-positive gastric cancer (NCT02901301).

OncLive: What are the biggest obstacles the community is currently facing in CRC treatment?

Do you notice sequencing challenges as treatment options expand?

What are some potentially practice-changing clinical trials ongoing in CRC?

Can you reflect on the data we’ve seen so far with immunotherapy in CRC and the potential role it could have?

Do you believe we will eventually see immunotherapy have that type of promise in pancreatic cancer?

How will immunotherapy be incorporated into the pancreatic cancer paradigm?

Moving onto gastric cancer, what is on the horizon?

Will basket trials made up of molecular profiles versus tumor type/stage be the way of the future?

Will chemotherapy forever have a role in gastric cancer treatment?

You presented some challenging cases at this State of the Science Summit. What do you hope the audience learned?

In an interview during the 2017 OncLive® State of the Science Summit on GI Malignancies, Hemphill provided insight on some of the challenges currently being faced in GI malignancies—specifically, colorectal cancer (CRC), pancreatic cancer, and gastic cancer—and how molecular profiles of tumors will dramatically change outcomes for these patients.Hemphill: It is a combination of trying to actually maximize cure rates. Also, we are trying to manage side effects of the chemotherapy regimens that we offer, and then hoping we can get a patient to become resectable, especially with liver metastases or lung metastases, as well. The challenge we face is after they’re resected and continue chemotherapy to try to keep a nice, durable response for as long as possible.There is quite a bit of nuance; a lot of it depends on how robust the patient is and how clinically sound they are. For a young patient, you are more likely to be a bit more aggressive upfront, whether it’s 1 to 2 liver metastasis where you can actually consider resecting versus more [advanced] disease for which you are thinking about a more palliative approach. These decisions are considered.For CRC, we are looking at second-line immunotherapies. Even trying to put immunotherapy in frontline is not a common scenario in CRC. You actually have the ability to be thinking along those lines, but doing dual immunotherapy in very specific situations has a lot of promise. We have a lot of clinical trials looking at that space right now.For immunotherapy in CRC, specifically for patients who are microsatellite instability-high—which isn’t that common—some of the preliminary data that has been looked at definitely looks like there is a pretty strong response. Hopefully, we are seeing fewer side effects in that realm of treatment instead of traditional chemotherapy.We have seen immunotherapy have more potential and more durable results in other tumors than in pancreatic cancer.It might be a combination of immunotherapies or immunotherapy with other agents. Immunotherapy alone would be much less likely to have a response.One of the areas that we looked at was in HER2-positive gastric cancer. This is not a very common scenario but, when we see it, the addition of trastuzumab (Herceptin) or other anti-HER2 agents definitely improves response rates and overall survival.Absolutely. In fact, 1 of my cases presented was exactly that. We presented a case on intrahepatic cholangiocarcinoma that had ROS1. We used crizotinib (Xalkori) and we got a very good response in a patient that was refusing all chemotherapy. But, this 1 pill showed more than a 50% reduction in the size of the tumor. Symptomatically, too, the patient is doing beautifully.We’re hoping to see more of a shift to change the landscape so that we don’t see some of these long-term toxicities from chemotherapy. It might be a combination of immunotherapy plus chemotherapy or immunotherapy by itself; immunotherapy has been a game changer for multiple cancer types and it continues to be.I hope that they learned that there are other options—it is a combination of the standard of care plus thinking along the lines of clinical trials because that’s the way we are going to advance the field.