ASCO 2015: Report from Day 1

Greetings from Chicago! I am here in the Windy City for the annual meeting of the American Society of Clinical Oncology (ASCO), and will be providing daily immunotherapy-focused updates from the scientific frontlines.

There is a lot to look forward to at this meeting in terms of immunotherapy. Our CEO, Jill O’Donnell-Tormey, PhD, provided a preview earlier in the week. Of particular note for patients and caregivers are the results of several large phase III trials of immunotherapy drugs in lung cancer and melanoma that have the potential to radically transform standard of care for these conditions. You’ll be hearing much more about these trials tomorrow and Sunday.

Today’s sessions were mostly educational, providing overviews of treatment strategies in a variety of cancer types—including acute and chronic leukemia, lung cancer, and kidney cancer. I’m going to focus on kidney cancer because it sets up nicely some of the main themes that are likely to recur throughout the meeting.

As Martin Henner Voss, MD, of Memorial Sloan Kettering Cancer Center, pointed out in his afternoon talk, immunotherapy for kidney cancer is progressing rapidly. There are several ongoing phase III trials that are directly testing immunotherapies against standard of care treatment—which in most cases is a targeted therapy such as bevacizumab (Avastin) or sunitinib (Sutent). These phase III studies follow promising earlier phase II trials that showed higher effectiveness of these immunotherapies compared to historical results with targeted therapies. The phase III studies will directly compare the immunotherapy to the targeted therapy in a head-to-head fashion. Monday morning we’ll get some clinical updates.

There is good reason to suspect that kidney cancer will be amenable to treatment with immunotherapy. For one, there are known cases in the medical literature of patients with metastatic kidney cancer who occasionally experienced spontaneous regressions of their cancer—implying that the body’s immune system already knows how to fight this disease.

And in fact, immunotherapies in the form of immune-stimulating cytokines have been used for more than a decade to treat kidney cancer. The cytokine interleukin 2 (IL-2), for example, can cause kidney cancers to shrink in approximately 10%-20% of patients, and provide durable remissions in a subset of these. But this treatment has unpleasant side effects and it is now considered more of a last resort.

Which is why results with newer immunotherapies, such as checkpoint inhibitors and therapeutic cancer vaccines, are so welcome. They are providing improved efficacy with fewer side effects (though there are still some).

As in other indications, the checkpoint inhibitors that everyone is talking about are PD-1 and PD-L1 antibodies. These drugs block molecules that serve as brakes on the immune system. By “releasing the brakes,” they enable the immune system to mount a stronger attack against the cancer.

Thus far, this approach seems to work best against cancers that the immune system can more easily recognize as dangerous or foreign. This includes cancers such as melanoma and lung cancer, both of which are known to have lots of genetic mutations (caused by UV rays and smoking, respectively). Although kidney cancer has a lower “mutational burden” than these cancers, it seems that the mutations that do exist in kidney cancer make for good immune recognition. Quality of mutations, Dr. Voss suggested, is as important as quantity in terms of immune recognition.

Another reason why this is good news for kidney cancer patients is that the current treatments that are standard of care in this cancer type—the targeted therapies—often do not provide lasting benefits. They may work for a while to shrink tumors, but the cancer eventually becomes resistant to the drugs and grows back. That’s because these drugs target one or another specific pathway in the cell; cancer cells mutate quickly and can evolve to get around these individual roadblocks.

But immunotherapies are different: because they treat the immune system rather than the cancer, they can generate an anti-cancer response that is as adaptive as the cancer is, changing along with it—and keeping it in check for sometimes many years.

I hope this was at least somewhat educational. Check back tomorrow for more updates from ASCO, including the results of an important clinical trial of checkpoint inhibitors for lung cancer.