PD-L1 expressions at baseline did not play a role in the efficacy of Xalkori in patients with advanced non-small cell lung cancer and ROS1 rearrangements.
Patients with advanced non-small cell lung cancer (NSCLC) who have ROS1 rearrangements benefited from receiving Xalkori (crizotinib; a tyrosine kinase inhibitor) as first-line treatment, regardless of PD-L1 expression at baseline, according to a study published in Lung Cancer.
A ROS1 gene plays a role in sending signals in cells and cell growth, according to the National Cancer Institute. A protein made by the ROS1 gene is a type of receptor, called tyrosine kinase.
“ROS1 is a driver that can be fundamentally responsible for driving the lung cancer growth,” added Dr. Sally York, during an interview with CURE®. “ROS1 as a driver is not technically a mutation, it’s a rearrangement, so it’s a break between the normal part of the ROS1 gene [and is] broken and put together with another protein, so that the ROS1 kinase is always on. It’s a continuous growth-promoting translocation, [meaning] it can rearrange and stick on to different partners.”
York is a thoracic oncologist and associate professor at Vanderbilt-Ingram Cancer Center in Nashville.
READ MORE: ROS1-Positive NSCLC Represents a Targetable Mutation for New Therapies
The Efficacy of Xalkori and PD-L1 Expressions in NSCLC
Of note, having ROS1 translocations in NSCLC is rare, and approximately “1% of patients who have non-small cell adenocarcinoma, specifically, have a translocation driver like this,” said York.
“In the ROS1 group in particular, there’s not a lot of study of that,” she explained. “Because it is rare, it is hard to come up with a group of patients who have ROS1 translocations. So, I credit the authors here [from the Lung Cancer study] … What they demonstrated here is that there’s not a lot of connection between PD-L1 and responses to [Xalkori] and I think that’s reassuring.”
PD-L1 is defined as a protein that helps regulate the body’s immune responses and is found in abnormally high amounts in certain cancer cells, according to the National Cancer Institute. In other words, cancer cells can hide using an “invisible cloak” because PD-L1 regulates the immune responses, York explained. When patients receive anti-PD-L1 drugs, it puts holes in the invisibility cloak so the immune system can see the cancer and fight it, she said.
Importantly, the authors of the study noted that the association between PD-L1 expression and the efficacy of tyrosine kinase inhibitors, such as Xalkori, has not been explored. So, determining that the status of PD-L1 does not affect the efficacy of tyrosine kinase inhibitors is reassuring for patients, York emphasized.
“It should be reassuring to patients because they all responded [to Xalkori],” she said. “I mean, there was a good response rate and good disease control rate for all of those subgroups in this study. So, whether [patients] had a low PD-L1 or high PD-L1, they all had good responses to the drug. That is another indicator that the immune system does not have a bigger role to play in patients with a specific driver mutation like this.”
Significance of Targeted Therapy and Sequencing for NSCLC
For patients with advanced NSCLC with ROS1 rearrangements, York noted that receiving Xalkori in the first-line setting makes a difference, even though PD-L1 doesn’t make a difference.
“It’s important to recognize how active these inhibitors are if the right target is found,” she said. “Then, [doctors] have a [better idea of] how patients are going to do and how they have better outcomes if [they receive] the right target and the right drug upfront.”
With targeted therapies, such as Xalkori, patients may have better quality of life because the side effect profiles are more tolerable than with standard cytotoxic chemotherapy, York emphasized.
However, sequencing is done in the beginning to determine which treatments patients can best respond to, she said.
“It’s important for [patients] to know that sequencing takes time,” York explained. “And that can be frustrating for a patient to feel, ‘Well, why aren’t you doing anything? Why can’t we start right now?’ and it typically takes a couple of weeks to get those sequencing results back.
“But in general, if it’s not truly a medical urgency, it’s in their favor to get the data to figure out what the best first treatment is going to be, they’re going to have better outcomes and have fewer side effects if we find the right drug for them.”
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