Researchers at Massachusetts General Hospital are developing a supportive care model to help advanced lung cancer patients better understand their prognosis after research showed that the optimism around precision oncology is making it difficult for oncologists and patients to have more sobering but realistic discussions about end-of-life decisions.

The research, led by Laura Petrillo, a palliative care physician at Mass General, explored how precision oncology treatments have changed communication between oncologists and patients about metastatic lung cancer prognosis. Petrillo and colleagues published a paper in Cancer last month describing their findings.

The study included 39 patients with metastatic lung cancer with an EGFR, ALK, or ROS1 mutation, along with 14 caregivers and 10 oncologists. Researchers conducted interviews with each person to learn how they communicated about lung cancer prognosis and recorded conversations between patients and their oncologists. Based on those interviews, the researchers identified several common themes related to patients’ expectations about treatment efficacy, how they made medical decisions, and the types of information they desired.

Based on this research, Petrillo and colleagues are conducting a pilot clinical trial to develop a supportive care framework for patients with metastatic, oncogene-driven non-small cell lung cancer, called POISE. That trial, funded by a grant from the National Cancer Institute, will have palliative care specialists meet with patients with long, uncertain cancer trajectories so they can discuss psychosocial issues and learn health-promoting behaviors.

In the Cancer study, the researchers found that patients felt hopeful or fortunate when their oncologists told them a targetable mutation was detected. However, some oncologists noted in the interviews that the hope patients feel when they learn they have a mutation targetable by a precision medicine can overshadow the reality that they have metastatic lung cancer, which is incurable.

“It’s very natural to focus on the positive, and then that reinforces itself and the conversation goes in a specific direction,” Petrillo said. “Some of the oncologists told us they have a mode of communicating about the future, and it’s a very hopeful mode, but then it can be hard to enter back into the ‘what if things don’t go as we hope’ conversation.”

Moreover, patients with a targetable mutation won’t all derive the same benefit — another point that may not be emphasized in the conversation. “This treatment paradigm with wildly variable outcomes is going to force us to think more carefully about how we’re presenting information about targeted therapies in the future,” Petrillo said.

In ALK-positive lung cancer, for instance, there are several drugs approved by the US Food and Drug Administration. Second-generation ALK inhibitors, Takeda Pharmaceutical’s Alunbrig (brigatinib) and Pfizer’s Lorbrena (lorlatinib), for instance, have shown to be better at reducing the risk of disease progression or death compared to first-generation ALK inhibitors, such as Pfizer’s Xalkori (crizotinib). For example, in the trial that led to Alunbrig’s approval in first-line metastatic ALK-positive NSCLC, 74 percent of patients on the newer drug had a reduction in tumor size compared to 62 percent on Xalkori. Lorbrena also outperformed Xalkori in a Phase III trial in the same setting, reducing the risk of disease progression or death by 72 percent versus Xalkori.

Although these drugs are improving patient outcomes, the research by Petrillo and colleagues suggests that the reality of eventual disease progression can get “lost in the hopeful messaging.” One oncologist said some patients were not prepared for the eventual reality of running out of precision oncology treatment options as their disease progresses, due to the initial optimism about targeted therapies. Another oncologist in the study noted they were working to reframe the conversations about lung cancer with targetable mutations to try to balance the optimism with continued recognition of the fact that patients have a serious, incurable illness.

The optimism and high expectations for precision therapy can cause other problems for patients down the road. They can be less forthcoming about side effects, have more difficulty making end-of-life decisions, or become wary of chemotherapy treatment. For example, some oncologists said their patients were hesitant to discuss their side effects on targeted therapy because they didn’t want to be taken off the drug, or because they were so glad they responded to the treatment, they didn’t feel the symptoms were worth mentioning.

“When patients eventually do get to the point of being unable to have further targeted therapy options, it can be hard to accept the transition to chemotherapy,” Petrillo said. “Oncologists in the study talked about how chemotherapy may be a really viable treatment option that could give people more time, but it’s seen as an inferior treatment because it’s so toxic and people have experienced the targeted therapies and had those high expectations prior to that.”

Meanwhile, as new drugs enter the market and continue to improve outcomes for lung cancer patients, oncologists are finding it difficult to gauge when it’s appropriate to bring up end-of-life discussions. One oncologist in the study noted that many ALK-positive NSCLC patients can live more than five years on targeted treatment, and as a result, prognosis and end-of-life care is often not part of the discussion at diagnosis.

“It’s a very different paradigm,” the oncologist said in the study interviews. “When do you readdress? … A natural point is at times of progression. But oftentimes, we have a really great second-, third-line treatment that somebody can get many years off of.”

On the other hand, the changing treatment landscape can also empower patients, Petrillo said. The study found these patients with targetable mutations were more engaged in education and advocacy about their disease. Some patients in the study even brought potential clinical trials to their oncologists after finding them in online communities or through advocacy groups.

“The feeling is that there could be something that comes out at any point that will buy a few more years [for these patients] and then maybe one of those new things will be a cure,” Petrillo said.

Lessons from palliative care

Going off the learnings from this study, Petrillo and colleagues are advancing the POISE project, aiming to develop a model that integrates palliative care with survivorship care to help facilitate conversations that ensure patients better understand their prognosis and the treatment landscape. Within this model, oncologists will take cues from palliative clinicians in discussing lung cancer prognosis with their patients.

While optimism about treatment can benefit patients, their hope should be grounded in the reality that advanced lung cancer remains an incurable disease. “It’s a real balance of both being hopeful with people [about the possibility of] a lot more good quality time, and then also gently introducing the eventuality of health changing over time and helping people be comfortable with that eventuality,” Petrillo said.

The lessons for palliative care can help doctors achieve this balance with patients. “In early palliative care, we can introduce things gradually and open these conversations over a long period of time, because it can be really hard to address in one single conversation or when the horse is out of the barn,” she said.

Petrillo also emphasized the importance of supporting patients’ emotional needs related to their diagnosis. Those needs vary between patients, with some actively seeing information about prognosis, life expectancy, and drug efficacy, while others want support to help them “live well” with their disease, such as exercise, nutrition, and psychological support for coping with uncertainty.

“There’s so much hopefulness around these therapies, but there also needs to be space for this prognostic awareness to develop in order for patients to have the opportunity to prepare and plan for eventual changes in their health,” Petrillo said.