“Opportunities to escalate therapies that work well in stage IV into what we consider a more curative setting...are exactly what we need to be looking for.” –Mark A. Socinski, MD
The treatment of lung cancer has evolved greatly over the last 30 years. Recently, numerous therapy modalities have been tested and successfully implemented into earlier stages of treatment as either adjuvant or neoadjuvant therapy. Additionally, clinicians across the cancer care paradigm are learning how to better tailor treatment to patients based on their genetic makeup.
In an interview with ONCOLOGY®, Mark A. Socinski, MD, reviewed recent updates in lung cancer and the progression of lung cancer treatment throughout his career.
Additionally, Socinski spoke about finding ways to cure lung cancer when patients have earlier-stage disease, and which updates from recent conferences have the most potential to impact the standard of care.
Socinski: I started [treating lung cancer] in the 1980s, when editorials were being written to debate whether lung cancer was a treatable disease. Some providers believed you should treat it, while others thought it was not treatable and people should just go on hospice. That’s where I started. Looking back over roughly 30 years, [it’s difficult to] believe the advances that we’ve made in lung cancer. Cancer mortality figures in the United States show the greatest annual reduction in cancer mortality that has ever been seen, and that reduction was largely led by lung cancer and melanoma. The greatest advance in the disease is the understanding of biology. When we say lung cancer, specifically non–small cell lung cancer [NSCLC], we’re dealing with up to 40 different diseases.
EGFR-mutant lung cancer is different from ALK fusion–positive lung cancer, which is different from disease that doesn’t have a genomic driver but has high PD-L1 expression. Being able to take that pie and divide it up into various pieces helps you understand why treatment is more of a personalized approach—[it’s] because of our understanding of the underlying biology. Lung cancer has become the poster child for targeted therapy, and that’s led to a benefit in overall survival [OS] in NSCLC. That’s been the biggest change over time that’s allowed us to select the right treatment for the right patient at the right time; [we] realize that not every treatment, or not every new drug, will work for everybody. Rather, it probably will work well in 10%, 2%, or 20% of the patients; you just have to be able to find those patients at [diagnosis]. We do comprehensive genomic testing. If a patient does not have a genomic driver, the next important thing is a high PD-L1 expression. We now have the option of giving immunotherapy with good results, so those have been the biggest changes over the years.
Socinski: As a lung cancer doctor, most of my career has been spent treating patients with stage IV NSCLC. I’ve counseled countless numbers of patients who have a treatable disease, but not a curable disease—but that’s changing. [Some] patients who we thought were not curable may be cured. Most of my colleagues in lung cancer believe that this is true because we see it. When you have advances in the treatment of stage IV disease and lung cancer screening that will identify patients at an earlier stage, we’ll hopefully see more of a stage migration in terms of when we treat patients. Most of my career has been spent treating stage III and IV diseases. If you look at breast cancer, patients are treated mostly at stage I or II, and we’d like to get [to that point] in lung cancer. Opportunities to escalate therapies that work well in stage IV into what we consider a more curative setting—the surgical setting, or the chemoradiotherapy setting in stage III disease—are exactly what we need to be looking for. We’re beginning to see some payoffs from the various trials. The data we have [so far] show that there’s a role for immunotherapy in the neoadjuvant or adjuvant setting, and there’s a role for osimertinib [Tagrisso] in the adjuvant setting with an EGFR mutation. We’ll see more of that as we move forward. We don’t know the data yet for adjuvant trials that are exploring other immunotherapeutic agents. This is exactly what we need to do because even though we think surgery cures patients, it’s not where it should be.
Socinski: In the first-line setting, the general answer to that question is no. I always say that a [targetable mutation] trumps everything. FDA-approved targeted therapies in the targeted population are much more efficacious than chemotherapy as well as immunotherapy. In general, the patients who have these targeted DNA alterations tend to be lighter smokers or nonsmokers. Although that’s not absolute, for the most part, immunotherapy is not very efficacious in these subsets relative to the targeted therapeutic options for patients. For patients with targetable alterations, most of them are given targeted therapy in the first-line setting. There are a couple of exceptions with alterations like KRAS G12C and EGFR exon 20 insertions, for which the standard of care is still first-line platinum-based chemotherapy plus or minus immunotherapy.
Socinski: Most of [the interesting data presented] were in early-stage disease. I had to give an ASCO review in July this year, and for the first time in my career, I started [the presentation by discussing] stage I surgical disease and made my way to stage IV at the end. It was a different approach, but it was mainly because from ASCO, the exciting data came from updates in adjuvant as well as the neoadjuvant therapies. Such updates included the CheckMate 816 [NCT02998528] and the NADINE [NCT03081689] trials.1,2 Those are 2 new trials of neoadjuvant therapy. [These trials] come on the heels of having an FDA approval [of atezolizumab (Tecentriq)] in the adjuvant setting, and much like the PACIFIC trial [NCT01693562], it resparked the debate about neoadjuvant vs adjuvant therapy and who’s the appropriate patient for each approach.3,4 This brings up interesting questions and makes us rethink how we’ll incorporate this into practice.
Socinski: We did see updated OS at the interim analysis for the IMpower010 trial [NCT02486718] looking at disease-free survival [DFS].5 We can debate the most pertinent end point in the surgical setting, but most of us feel that it is OS, not DFS. Yes, there is nobility in delaying the recurrence of the disease, but you do surgery to cure the disease. Are we improving the cure rate? That is still a somewhat unanswered question.
An update was presented regarding the IMpower110 trial [NCT02409342] that looked at the OS advantage.6 These high PD-L1 expressors appeared to have a promising OS benefit. At least in those patients with greater than 50% PD-L1 positivity and node-positive disease, immunotherapy is going to improve cure rates, which is what most of us want to see. We have a number of these trials ongoing. Like an HBO miniseries, whether we’re in season 1, 2, or 3, we have to wait for it to play out.
Socinski: It was a combination of opportunity and mentorship. When I was a fellow, there was an opportunity in the lung cancer program at the Dana-Farber Cancer Institute where I was trained. No one else wanted to do lung cancer, so that was my opportunity. It just so happens that one of my favorite attendings oversaw the lung cancer program, so he was my mentor. I viewed it as an opportunity to match with a mentor, and that’s what drew me to lung cancer. I refer to those times as the dark times of lung cancer because we used relatively toxic therapy, which at that time was providing minimal benefits compared with what we can do nowadays.
Socinski: We throw around the term “pracademic,” a combination of practice and academics. Academic medical centers have pros and cons. I trained in an academic medical center where I had 20-plus years of experience, so I understand the beast, as they say. But you don’t need an academic medical center to build a cancer program. At AdventHealth, we’re slowly accumulating people who have had successful careers in academic centers who are looking for a different model. I’ve been impressed with the quality of clinicians that we’ve been able to recruit since I’ve been here. If you look at the latest US News and World Report [rankings], for the first time in a long time, AdventHealth Cancer Institute was ranked [quite high, at] 30th. This reflects how we’re building and how we’re putting the processes and procedures in place to treat cancer in a way that’s recognized. In my position as AdventHealth Cancer Institute’s director, [I believe] there’s no reason that we can’t be as good as every academic medical center, even a Comprehensive Cancer Center. That’s what we aspire to.