Q+A: Catherine Shu, MD, on the State of Lung Cancer Treatment and Research
Lung cancer (both non-small cell and small cell) is the second most common cancer in both men and women in the U.S. While each year the number of new lung cancer cases decreases, partly due to the heightened awareness of smoking and improved treatments for the disease, lung cancer remains the leading cause of cancer death among both men and women worldwide, comprising 25% of all cancer deaths.
A physician-researcher in thoracic oncology, Dr. Catherine Shu has a focused interest in improving outcomes for lung cancer patients with resectable disease, specifically on investigating neoadjuvant therapy—treatments given to a patient prior to surgery. Dr. Shu is a member of the Herbert Irving Comprehensive Cancer Center (HICCC) and clinical director of the Thoracic Medical Oncology Service at Columbia/NewYork-Presbyterian.
“Lung cancer has a higher rate of recurrence than many other cancers, and one of the ways we are addressing this is through neoadjuvant therapy,” says Dr. Shu.
In a study published in Lancet Oncology, Dr. Shu and study coauthor, Dr. Naiyer Rizvi, demonstrated the safety and efficacy of a novel combination chemotherapy-immunotherapy regimen prior to surgery in patients with resectable non-small cell lung cancer. The patients enrolled in the trial, initiated at the HICCC with sub-sites at Massachusetts General Hospital and Dana Farber, presented a high percentage of major pathological responses with manageable side effects, and the trial has since advanced into a global phase three trial.
“So far, immunotherapies have only been approved for metastatic lung cancer, or cancers that have spread to other parts of the body, so many patients with localized or regional lung cancer have not been able to use these newer treatments,” says Dr. Shu. “It’s very exciting to have initiated this trial here and to be able to add a new promising, pre-surgical therapy for a whole subset of patients to potentially improve survival rates and limit recurrence.”
Can you explain the types of lung cancer?
We separate lung cancer into two main categories, into non-small cell lung cancer and small cell lung cancer. And then under non-small cell lung cancer, there are additional subtypes, categorized based on the way the cancer looks under the microscope. So, there's adenocarcinoma, there's squamous cell carcinoma, and there are other types. It's important for us to know the exact subtype of cancer because that changes the way we treat them. The treatment is dependent on the stage and the exact diagnosis.
Small cell lung cancer, which tends to be smoking associated, tends to have a worse prognosis. It’s a very aggressive form of lung cancer.
What has been a key advancement in the field of lung cancer?
Definitely a key advancement in lung cancer that we’ve seen in the last 5 to 10 years is molecular testing and genotyping. We do a lot of molecular testing in lung cancer. It’s a very important part of our treatment because there are certain driver mutations that are targetable with available medications. The most common targetable mutations in lung cancer are called EGFR and ALK, and we have drugs that work exceptionally well against those targets.
Finding out those targets and then discovering drugs that can match those targets has been an important part of lung cancer research because we've been able to give patients medications that are not only tolerable but also very successful at disease control for an extended amount of time. Some of our patients don't get chemotherapy anymore because they're able to get these targeted therapies. Lung cancer has definitely advanced significantly in terms of better treatments.
What are some of those better treatments?
Over the last five years, immunotherapy has been a very exciting new type of therapy to watch unfold. It is a therapy where we use the patient's own immune system to fight the cancer, as compared to chemotherapy, where we give patients toxins into their bloodstream to fight the cancer.
Sometimes, the tumor can sort of “trick” the immune system into ignoring the cancer as it continues to grow. With immunotherapy, we can wake the immune system up, and then the immune system can attack the cancer. Immunotherapy is generally less toxic than chemotherapy, so patients typically tolerate it well. Patients who respond can have a long response. I have some metastatic patients who received immunotherapy and are now disease free and have stayed that way for years; this would have been unheard of years ago.
What else is having an impact in the area of lung cancer treatment?
One of the really interesting technologies coming out is something called ctDNA or circulating tumor DNA. The technology is now at that point where if a patient’s tumor is shedding DNA into the bloodstream, we can sometimes pick that up using a “liquid biopsy.” You could imagine this could be used in a variety of ways, either to detect recurrence or to risk stratify patients. There are many trials and studies now looking into uses of ctDNA; I think it will be an important part of the future.
And with immunotherapy, we’re learning all the time. We’re constantly learning which immunotherapy drugs work well together. How do we increase the response rate? How do we lengthen the progression-free survival? Which combinations might have less toxicity and fewer side effects for patients? These are all questions that we have and that we continue to investigate.
Before targeted therapy and before immunotherapy, everyone got the same chemotherapy. We have better drugs and targeted therapies now and also a huge improvement in technology. For example, our radiation oncology colleagues have newer machines and are able to develop new treatment plans. We’re always learning, and our goal is to provide better, more tailored treatment for our patients.
What challenges remain for lung cancer?
The five-year survival rates are still pretty dismal. Particularly for patients with localized or regional, non-small cell lung cancer, the five-year survival rate can still be anywhere from 30% to 60%, which, if you think about it, is unacceptable. Improving these numbers is the reason I am working on these neoadjuvant treatments and trials. Our lung cancer patients will still need to have surgery, but if we can lower the rate of recurrence, if we can improve their survival, if we can cure more patients, then the hard work is definitely worth it.