ASCO [American Society of Clinical Oncology], the preeminent medical meeting focused on cancer, took place at the start of June. It’s exciting to observe some of the promising innovations/drugs that had clinical trial data there.
There are two noteworthy trends in cancer therapy. First, as human understanding of cancer has evolved, we are increasingly able to characterize the genetic mutations driving a tumor. Lung cancer, it turns out, is not a single disease. Rather there are hundreds of different mutations that can lead a normal cell to transform into a cancer cell. As we identify these mutations, we also map out the mutant harmful proteins that are made (these proteins are generally “growth” proteins that tell a cell to grow uncontrolled instead of simply maintaining its normal structure and function in the body).
With this knowledge in hand, companies are designing drugs to target these mutant proteins. This remains an iterative step forward, as these new drugs are not cures. However, they are producing responses (tumor shrinkage) and prolonging life by several months in select patients. Further, this type of advance is beneficial to the healthcare system overall, as doctors can test the genetics of a tumor and select drugs that specifically target the bad-actor gene. This is more efficient and often less toxic than the current paradigm of using nonspecific chemotherapy (poisons that kill fast-growing cells, which is the hallmark characteristic of cancer cells).
Beyond these new targeted chemotherapies, a new class of therapies called immuno-oncology (or “IO”) has captured the attention of both investors and clinicians. IO attempts to channel the body’s immune system to attack cancer. This had long been a goal of scientists with almost universal failures. Until now, scientists worked to develop vaccines using either actual pieces of tumors or alternately proteins known to be associated specifically with tumors. The hope was that these vaccines would ‘teach’ the immune system to recognize and then fight cancer. There have been hundreds of trials and not a single success of note.
In the last few years, IO has taken a leap forward. Scientists have learned that many tumors express a surface marker that ‘repels’ immune cells. In other words, tumor cells are effectively cloaked even if the immune system is looking for them. A new class of IO, PD-L1 inhibitors, blocks this cloaking mechanism. Two new drugs of this class were just approved by the FDA: Opdivo (from Bristol Myers [BMY]) and Keytruda (made by Merck [MRK]). These drugs have been shown to be effective in melanoma and lung cancer. Clinical trials in multiple other tumor types are underway. These agents appear to offer incremental benefits rather than cures, but scientists are looking to find even better compounds and explore combinations of therapy that could be even more effective.
These are meaningful steps forward. This is promising and exciting science playing out as we watch.
Sources:Europe PubMed Central, “PD-1 Blockade in Tumors with Mismatch Repair Deficiency”; New England Journal of Medicine, “Pembrolizumab for the Treatment of Non–Small-Cell Lung Cancer”; New England Journal of Medicine, “Nivolumab and Ipilimumab versus Ipilimumab in Untreated Melanoma”; New England Journal of Medicine, “Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma”