Solange Peters, MD, PhD, Reviews Evolving Treatment Trends in Lung Cancer

Oncology, ONCOLOGY Vol 36, Issue 6, Volume 36, Issue 6
Pages: 348-349

“Be courageous: Your work will be recognized, and everything is about [the] work in the end.”

Creating a more diverse workplace for lung cancer clinicians, especially those participating in clinical trials, has been a main focus in the oncology space in recent years. Additionally, clinicians are learning how to better stand out in the field, and to speak up and be recognized.

In an interview with ONCOLOGY®, Solange Peters, MD, PhD, spoke about recent research trends and the biggest obstacles in lung cancer that specialists face today.

Peters also detailed how HER2 mutations have led to developments in lung cancer treatment and discussed barriers to molecular testing. Further, she shared advice for those trying to break into the lung cancer field.

Q: What trends have you seen so far, and do you expect to see, in 2022?

Peters: Lung cancer [used to be in the] category of diseases with very poor outcomes. Using traditional surgery, chemotherapy, and radiation, lung cancer outcomes were disappointing. [Now], 2 big chapters have dramatically changed the fate of [patients with] thoracic malignancies. The first chapter is molecular biology: trying to understand and discover the gene, or oncogene, [that is causing the cancer. The discovery] of the oncogene leading to the malignant phenotype has led to a portfolio of targeted therapy.

[Also included in] the first chapter are molecular characterization, oncogene addiction, and targeted therapy, which started [about] 15 years ago with the EGFR mutations. Now we have 15 [driver] mutations that we can treat without chemotherapy or radiation in first- or second-line treatment, [using] targeted therapy. This has been moving progressively in the last 15 years, and we’re [continuing to keep] pace by discovering new compounds or new targets. [However], the low-hanging fruit might have been caught. What we improve every time we can is the pharmacology of the targeted therapies. We have been handling more potent drugs in terms of preventing resistance.

The second chapter involves immunotherapy, which has led to long-term survival for some patients with lung cancer despite metastatic disease. When I started out, I couldn’t conceive that patients with metastatic disease could survive years, but now [they can], with immunotherapy. We have strong data showing that immunotherapy should be used alone or in combination with chemotherapy in all metastatic disease in the frontline. However, these immunotherapies are now moving to early-stage disease, [such as in those cases with] small nodules that are resected and are treated with curative intent. The first data [have been presented from] 3 trials already. This year, there will be many more trials in early-stage disease. These trials show that immunotherapy has a place and a role in early disease, [along] with surgery and any kind of radical treatment. That’s a revolution, not only in lung cancer but also in other cancer types. In lung cancer, we can combine immunotherapy with the old strategies to [potentially] cure patients.

Q: What are some barriers and issues surrounding molecular testing for early-stage disease?

Peters: Unfortunately, if you look at the picture of molecular testing in Europe, fewer than half of patients have access to decent testing. Among [those who do have access], some have very minimal [testing]. Fewer than half of patients have a tumor that is characterized in terms of targets. That’s probably where most advances are needed, because [the current situation] creates unacceptable inequities in cancer and in the cancer journey.

Q: How have HER2 mutations emerged as a relevant target in lung cancer?

Peters: It’s interesting, because it’s a journey lung cancer specialists have taken because of breast cancer. We don’t treat the same HER2 alteration in lung cancer. [In breast cancer, they treat] what we call amplification, which also translates into an overexpression. What we speak about in lung cancer is mutations. It’s a modification of the protein. Usually, it’s an insertion within exon 20 of the gene. This is the alteration that we target in lung cancer today.

We tried to use breast cancer drugs like trastuzumab [Herceptin] and compounds like poziotinib, which have given rise to activity. When trying to make a risk-benefit assessment, [however, we found that] none have [achieved efficacy that is significant enough to] consider them the standard of care. Sometimes the toxicity of such compounds can be very high.

Until now, there was no standard option for HER2 mutations in non–small cell lung cancer. Then suddenly came an idea from this new generation of agents: antibody-drug conjugates. A very important agent, called the payload, is conjugated with a specific antibody, very similar to trastuzumab. Based on that, you can deliver therapy to the right place. T-DM1 [trastuzumab
emtansine; Kadcyla] has given rise to wonderful results in breast cancer, but also in lung cancer. This is where you reach a threshold with close to a 60% response rate. It might be later and down the road [that it is] recognized everywhere as a second-line treatment, but I would even say [it will be] a frontline strategy for our patients. Suddenly, we’ve gone through these limitations, and we have [found] an option.

Q: What key research trends do you find most interesting?

Peters: We are trying to cure more patients; that’s what differentiates us from breast cancer specialists, [who are currently better able to cure patients]. When breast cancer specialists treat with chemotherapy, hormonal therapy, and surgery, they get to cure. The curves in breast cancer survival are high, between 80% and 100%. In lung cancer, when you perform surgery and chemotherapy, only half, maybe about 40%, of the patients will be cured. Even in lung cancer with all the specialists, curing the disease [is a challenge]. We will do more screening for lung cancer and start to implement programs for heavy smokers with regular CT scans, which will lead to stage migration—from advanced to early disease. You will have more early disease documented, and better treatments [available]. If you keep these advances together, it will revolutionize in how lung cancer will [become] a curable disease, or at least more curable.

Q: What advice do you have for up-and-coming oncologists?

Peters: First, oncology research and an academic career are a commitment. You need to commit to long hours of work, [although] it doesn’t mean there are no hobbies or family. It’s about the amount of work and loving it. You need to really feel like doing it and [committing to] a heavy [workload].

Second, you need to find a mentor. A mentor will put you on the scene and, [for instance], give your name to give a talk. Even if you deserve it, somebody has to show to the community that you are very good. Find a mentor where you [work]—or even somewhere else, because lots of mentorships can be [remote]—but find a mentor to help you.

[Lastly], everything is about choices. You must make good decisions. Diversity is my main goal as ESMO president. Try to understand that wherever you come from, or whatever your gender, preference in life, and trends in decision-making, you can make a career. [When I first began my career], there were [almost] no women in the field. The picture of gender has changed quite a bit. You need to be well surrounded by vocal [colleagues] and you need to make yourself seen, even if sometimes it might be a little shaky in the beginning. Be courageous: Your work will be recognized, and everything is about [the] work in the end.