Rethinking cure in cancer treatment

We live in fortunate times. In our history, there has never been a time when more therapeutic approaches have existed to help patients with cancer. For as many treatment options as there are now, even more are on the horizon, potentially offering hope to the millions who receive this diagnosis and immediately fear the future.

Multidisciplinary treatment, combining surgery, radiotherapy, and medical therapy, is curative for many patients with early cancer. Even for some types of advanced cancer, long remissions can be achieved. The tumor cells are significantly reduced and do not return over a period of years – 3 years, 5 years and even 10 years, depending on the type of cancer and how aggressive it is. But this is not true for the majority of advanced cancers, and we know that there are tumors that can come back even after that 10-year timeframe.

What did those years mean for the patients whose cancer returned? Were their lives relatively normal during that time? Were they essentially living with a chronic disease? This could be a starting point to reframe how we think about “cure” and what constitutes successful outcomes in the context of cancer.

Perhaps an appropriate analogy is HIV. When patients were diagnosed with HIV in the 1980s and early 1990s, death was virtually certain because there were not yet effective medicines to treat it. With the introduction of protease inhibitors in the mid-1990s, followed quickly by a number of additional types of medicines, HIV went from a death sentence to a chronic disease, allowing those infected to live relatively healthy lives.

So, could this also be a goal for many cancers? The question turns us to a discussion about what constitutes a successful outcome. If we were to ask health care professionals, regulators, patients and others what they believe is the right type of benefit to receive from cancer treatment, we would get many different answers.

Classically, shrinking the tumor is the one most people think of first. But more important are the outcomes used for registration of new medicines and validation of other types of treatments, and those are extending patient survival from cancer and extending the survival of patients without cancer progression. This doesn’t necessarily mean the tumor goes away. In most cases, it means the patient is continuing to live, in spite of the disease, with chronic cancer.

A lot of the discussion around the chronic treatment of cancer has been stimulated by the emergence of targeted medicines. These are not chemotherapy or radiation, which generally work by destroying large masses of cancer cells but also destroy normal tissue in the process. Neither chemotherapy nor radiotherapy distinguishes tumor cells from healthy ones.

AbbVie and others are developing targeted medicines, which are designed to address very specific attributes of a particular disease. For example, they might be programmed to find and block the function of one protein that is a known disease driver. By selectively engaging only this protein, healthy tissue is potentially spared while tumor tissue is destroyed.

One theory about cancer treatment that has come about using these therapies is that a targeted therapy could reduce or stop the growth of a tumor, or even eliminate many cancer cells, for a long period of time. However, we’ve seen that resistance to these therapies may develop in the remaining cancer cells. That resistance may be because a genetic defect that was present in a small fraction of tumor cells allows those cells to escape the targeted therapy, and that small fraction takes over where the other cells left off.

Ideally, another targeted therapy could address this second population, greatly reduce the number of tumor cells, and extend life for patients. Because of the targeted nature of these treatments, this type of approach could be repeated, addressing different mutations with appropriately targeted treatments. Patients could effectively be cured by preventing symptoms or progression despite chronic low-level disease.

As a clinician, I want patients living with cancer to feel confident in their future, knowing that living normally with the disease for decades is possible. We’re not there yet, but with the incredible amount of ongoing research, coupled with the many new treatment approaches we will see in the coming years, I believe it will happen.

One day, we will eliminate cancer. Until then, we might consider a more flexible definition of “cure” – one that says although the cancer hasn’t been entirely eradicated, it is not going to affect a patient’s ability to live a normal life.