Changing Lives With Immunotherapy

WHEN IT COMES to gastrointestinal (GI) cancers, there’s quite a disparity in the gains that research is bringing us. In some of these diseases, such as cholangiocarcinoma, scientists are diligently searching, but are so far finding that new solutions for prolonging survival remain elusive. In other intransigent cancers, such as colorectal, gastric and esophageal, immunotherapy is offering glimmers of hope.

It’s a trend that inspires optimism across the spectrum of GI cancers, as immunotherapy is being investigated in many of these diseases. That’s why we’re looking in-depth at this topic within the pages of our gastrointestinal cancers special issue.

In an article on immunotherapy in GI cancers, we explain that inhibitors of PD-1 look particularly promising in colorectal cancer. Interestingly, one subset of patients with this disease has had the best outcomes with the PD-1 inhibitor Keytruda (pembrolizumab) — those with mismatch repair deficiency. This glitch prevents cancer cells from repairing damage they have experienced, and because this results in the accumulation of a large number of mutations, it makes the cells more easily visible to the immune system. Helped along by Keytruda, early studies have shown, the human body can do an admirable job of rooting these cells out.

In esophageal cancer, both Keytruda and an experimental PD-L1 inhibitor are showing promise. So far, the best candidates for treatment with these drugs seem to be patients whose tumors express PD-1 and, more generally, those with cancers of the upper GI tract. For one patient whose story is told in this issue, the investigational PD-L1 inhibitor durvalumab sparked a complete remission of stage 4 esophageal cancer, something he calls “an absolute miracle.”

Similarly, the article explains, another biomarker for success with immunotherapy, particularly in gastroesophageal cancers, is the expression of PD-L1 by tumors. Patients who have this type of disease have demonstrated responses to the anti-PD-1 drug Opdivo (nivolumab).

An advantage of these drugs is that they tend to cause only mild side effects.

Researchers are endeavoring to boost the performance of these drugs in eligible patients by combining the treatments with other immunotherapies; for instance, Opdivo is being paired with Yervoy (ipilimumab), an immunotherapy that targets the protein CTLA4, in an early trial of patients with colorectal cancer. Another tactic involves combining immunotherapies with targeted drugs such as Herceptin (trastuzumab) for those whose tumors overexpress the protein HER2, or with anti-angiogenic drugs, which stop the growth of blood vessels that support tumors.

Long-term, the hope is not only to cement the benefit of immunotherapies in these populations, but to extend their effectiveness to much broader groups of patients who have GI cancers. An ever-growing understanding of the genomic factors that drive these cancers should help pave that path.

We hope that the insights offered in this issue — not only about immunotherapy in GI cancers, but also about other emerging treatments for GIST, cholangiocarcinoma, pancreatic and gastric cancers — will leave you feeling better informed about the state of research and treatment in this field.

As always, thank you for reading.

MIKE HENNESSY, SRChairman and CEO