Navigating Fertility and Pregnancy Challenges in Young Patients With Lung Cancer

An increasing number of young women are being diagnosed with lung cancer. According to Narjust Florez, MD, this highlights the lack of data and guidelines available for fertility and pregnancy in these patients.1

Historically, lung cancer has been known to be a disease that affects older individuals. But since 2018, more young women compared with men are being diagnosed with lung cancer, presenting unique challenges in managing fertility and pregnancy.^1,2

“We are getting younger and younger patients diagnosed with lung cancer,” Florez, associate director of the Cancer Care Equity Program and a thoracic medical oncologist at the Dana-Farber Brigham Cancer Center, told Targeted Oncology^TM in an interview. This shift has shown there to be a gap in the current understanding and management of fertility and pregnancy among patients with lung cancer. Florez noted that this has also contributed to significant delays in diagnosis and treatment.

One of the key concerns for young patients with lung cancer is the impact of cancer treatments on fertility. According to Florez, “when you look at all the data in lung cancer, there is no analysis in fertility whatsoever.” This is because most of the existing studies provide little, if any, insight into the real effects on fertility in humans.

With this knowledge gap, several studies have been initiated, including FINCH, which is being investigated by Florez and aims to evaluate the fertility effects of lung cancer drugs on patients.

In the interview, Florez shared insights into these emerging issues and the urgent need for tailored guidelines and research.

Lung with cancer cells: © catalin – stock.adobe.com

Targeted Oncology: Can you provide some background on your work regarding fertility and pregnancy in young patients with lung cancer?

Florez: What is happening in lung cancer with young [patients] is we are getting younger and younger patients diagnosed with lung cancer. For the first time ever, so [from] 2018 onwards, more young women are getting lung cancer than young men. The issue with this is that we do not fit the box for what a patient with lung cancer is. That leads to delays in diagnosis, women being gaslighted, which leads to diagnosis of advanced stage [disease]. As we continue to understand this journey of young patients with lung cancer, I realized that as patients are being diagnosed at a younger age, we are going to encounter 2 things: fertility and pregnancy.

When you look at all the data on lung cancer, there is no analysis in fertility whatsoever. There is no data. I was meeting with this young woman in my clinic because I specialize in young patients and they were like, what are the effects of fertility? And I went back to literature, and I had no idea. Most of these agents were tested in sexually immature animals. And they are saying this is bad for fertility, but the animals were not, again, sexually mature. They were artificially made pregnant, artificially stimulated, [and there were] very limited studies. So, I am talking to these women who go on these therapies for a year because they have curative intent, but I have no idea about fertility.

That prompted a lot of studies, including [one] called FINCH, which is evaluating fertility effects or drugs in patients with lung cancer. But then as I started doing this work, I got a phone call that potentially changed my life forever. It was, “I need your help. I have a young woman that is pregnant that has lung cancer.” I still talk about that and still get chills down my spine, and I am the one who treats more pregnant women with lung cancer in the world.

Can you explain the challenges and lack of guidelines?

This is a new issue. We have younger women that are pregnant and being diagnosed with lung cancer, and there are zero guidelines. There is no information. So, what happens is that people are treating these young women with a protocol that was created for people that are not pregnant. That is leading to fetal consequences and maternal consequences. A lot of these targeted therapies that we use in lung cancer affect the fetus. A lot of these genes that are inhibited by these targeted therapies are essential for fetal development. Like the ALK gene is essential for tooth development, so if you put a patient on an ALK inhibitor that crosses the placenta, potentially, the fetus will not develop brainstem, and it will not be viable at the time of delivery. Viable means they die immediately once they are out of the vaginal canal.

That led to more questions. What about treatment of EGFR patients? We launched the registry in December because there are 0 guidelines for these patients. When there are no guidelines, what happens? Everybody does a different thing. The outcomes are hard to measure. Also, you are not only messing up one person’s life; you are messing with their offspring. For many of these young women, that will be the last time they are pregnant.

Can you further discuss the registry that was created?

We created the registry, and in a Cancer article, you can learn about the registry. We created the registry to capture these cases, and we already have the first presentation at a conference. We have an oral presentation, and we have a poster about outcomes of pregnancy in young patients with lung cancer. It is the first systemic review. There always have been case reports, but we are putting all together and presenting to give guidelines to everybody around the globe because this is not only an issue in the United States. Younger patients with lung cancer have become an issue since 2018 in Brazil, Canada, Spain, France, Italy, India, Australia, China, Japan, and it is a global issue.

When you ask 1000 women walking in the street, what is the number 1 cause of cancer deaths? None of them say lung cancer. One percent of that 1000 patients [according to a] study that was done. So, what happens is that there is no awareness. People do not think about it. The doctors do not think about it, the patients do not think about it, and when younger patients come to get treatment, we need to first know how to treat pregnancy in lung cancer. Second, what affects fertility? Are you condemning these women to not have children because you do not give them the information? The scary part is that this happened in breast cancer 20 years ago. We just do not learn medicine from previous experiences.

The article focuses on the incidence of young lung cancers going on the rise. We are seeing more pregnant women with lung cancer than ever before. There are no guidelines. And third, we are not providing real informed consent to these patients. Because if we do not have data about fertility, how can you consent to something? Let’s say you asked me, Dr. Florez, what are my chances of getting pregnant after this? And my answer is like, I do not know, there is no data. Are you really consenting to this? You are not. And to be honest, it is borderline unethical. We are really working, the first author and I, very hard on getting this done because we are young women, and we have a lot of young patients, and we want to make it happen.

How has the incidence of lung cancer in young adults changed in recent years?

Since 2018, for the first time in history, young adults are getting more lung cancer than the average patient. This is irrespective of tobacco use or tobacco behaviors. There is an increased incidence in people with no smoking history. There has to be an underlying mechanism that we are trying to investigate that is causing all of this. Because why are these women getting more lung cancer? We have several theories. I have a large study; it is the largest study today, in which we are hearing the young patients, and we are interviewing their mothers. We are doing genotyping to understand why this is happening. These are young women with no previous tobacco use, but the cancer has such a big stigma that it is not in the news. And it is the number 1 killer. We prefer to talk about sarcoma, which is way [rarer].

What are just the risks for pregnancy in young women with lung cancer? Can you just talk about the way that targeted therapy has changed the outlook?

The issue is that targeted therapies should not be used during pregnancy because they will cross the placenta. So, we should discourage this. But it allows patients to go to the appropriate therapy immediately after delivery. I found myself running in the hospital with a bottle of alectinib [Alecensa] for my patient that just delivered a baby. Sometimes the placenta is not even out, and I am like, pop the pill, we waited 3 months for this! Because I could not give it to her when she was pregnant. But the benefit of target therapy is that the moment this woman delivers the baby, I can start the treatment. If it was chemotherapy, I would need to wait for her to heal from the delivery for 2 to 3 weeks, the patient is going to feel awful, and with a newborn it is not doable. But with targeted therapy, I can even start the date of delivery so that women can have as normal a life as a new mother. Because they do not have to come and see me. They can spend the first month at home with their baby taking their tablets. The first month is so important for bonding between the mother and the child, and that is what targeted therapy allows.

Also, it allows these women to see a future with children. Before they knew that they had 6 months. That was it. Now, I have patients where their kids are toddlers. That is something that targeted therapy gave these young women. I have a patient right now where we just want her to see the kid at 1 year, and the kid just graduated from kindergarten on Monday. That stands to targeted therapy.

But the summary is, targeted therapy allows us to understand that women can have active treatment after delivery, understand after you find the mutation, and allows us to know how the cancer will behave when you have the gene. When you identify the gene, you know how the gene will behave, so you can predict during pregnancy. The patient can start cancer treatment right after pregnancy; the placenta does not need to be out of the woman. I have done it. The placenta takes 30 to 40 minutes to be delivered naturally, so if I make it to my patient first, they pop the pill first. It allows a woman to go home, be with their children, take a pill, and most importantly, to live long enough to see the children grow, because every woman deserves that if that is what they want to do. That is what target therapy does. But the health care system is not ready by any means. We just approved targeted therapy for osimertinib [Tagrisso] in the adjuvant setting, so these patients are going for curative intent, and alectinib. And we do not know what effects there are on fertility with those drugs. Nothing. So, I am doing a large study to do that. But it is quite concerning.

What are the key takeaways from this discussion regarding fertility and pregnancy in young women diagnosed with lung cancer?

The incidence of lung cancer in young patients is increasing every day and the health care system needs to be prepared so that we do not make mistakes that other tumor types have made.

REFERENCES:

1. Peccatori FA, Florez N, Imbimbo M. From approximation to precision: fertility and pregnancy questions in young patients with lung cancer. J Thorac Oncol. 2024;19(6):852-854. doi:10.1016/j.jtho.2024.02.005

2. Florez N, Kaufman RA, Yáñez-Sarmiento A, et al. When the unimaginable happens: Lung cancer diagnosis during pregnancy. Cancer. 2024;130(11):1905-1909. doi:10.1002/cncr.35227