Updated September 19th, 2023

Who Benefits from Immunotherapy in Lung Cancer? More Patients than Previously Thought, According to New Research

A new analysis shows that, among patients with metastatic non-squamous non-small cell lung cancer, the benefits of immunotherapy hold true regardless of the presence of a KRAS mutation.

Caroline Hopkins SurvivorNet

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Immunotherapy and Lung Cancer -- Who Can Benefit

A major new study recently showed that there was a survival benefit with immunotherapy alone (rather than with chemo) for patients with a certain type of lung cancer.
Now, a new analysis shows that that group of patients may be larger than previously thought.
Specifically, these patients can benefit from the drug regardless of whether they have a genetic mutation called KRAS.

The revolutionary new class of immunotherapy drugs called checkpoint inhibitors has revolutionized treatment for a common subtype of lung cancer, called nonsquamous non-small cell lung cancer. Recently, a major new clinical trial found that certain patients with this lung cancer could benefit from taking a type of checkpoint inhibitor called pembrolizumab (known by its brand name, Keytruda) on its own. This news was a big deal, since it showed that the drug had a survival benefit even without being combined with chemotherapy.

Now, data from a new followup analysis shows that more patients can benefit from this drug than previously thought.

According to the data, patients with this type of lung cancer that is metastatic — meaning it has spread beyond the lung — can benefit from treatment with Keytruda instead of chemotherapy, and they can benefit regardless of whether they have a genetic mutation called “KRAS” on their lung cancer tumors. Before this analysis, previous studies had suggested that having a KRAS mutation on your lung cancer could make you less likely to benefit from Keytruda.

Importantly, to benefit from Keytruda, lung cancer tumors have to express something called PD-L1, which is a signal on the cancer cell with which Keytruda interacts.

“These data are preliminary, but confirm that patients with KRAS mutations benefit from treatment with pembrolizumab [Keytruda] vs. chemotherapy,” Dr. Gilberto De Lima Lopes, a lung cancer researcher at Sylvester Comprehensive Cancer Center at the University of Miami and the Miller School of Medicine, tells SurvivorNet. The news was presented at the European Society of Medical Oncology’s recent immunotherapy conference.

According to the analysis, the median overall survival (meaning the average amount of time that someone lived after starting the treatment) was significantly higher with Keytruda alone than with chemo — and that was true for people with and without KRAS mutations.

The Importance of Genomic Testing in Lung Cancer

KRAS is one of several genetic mutations that can better inform how well someone with lung cancer should be treated. The presence of mutations — including ALK, EGFR, and a number of others — can help oncologists decide the best course of treatment for a specific person’s cancer. Discovering these mutations and the role they play in how well someone’s cancer responds to treatment has been a major focus in lung cancer treatment.

Because the presence of these mutations can influence treatment decisions, experts often stress to SurvivorNet just how important it is to get genomic testing done.

“All patients with metastatic non-small cell lung cancer should have genomic testing and therapy should be tailored accordingly,” Dr. De Lima Lopes said.

Dr. Ronald Natale, director of the Lung Cancer Clinical Research Institute at the Cedars-Sinai Medical Center, explained the process of genomic testing in a previous conversation with SurvivorNet. “Today when a patient comes in with lung cancer, the first thing we do is next-generation sequencing on the tumor. We extract the DNA from the cancer. And we specifically search for hundreds of different mutations [that can inform treatment decisions]. We also test their tumors for the production of PD-L1.”

Dr. Ronald Natale spoke with SurvivorNet about how genetic testing can help determine treatment decisions for lung cancer.

“This is what we call precision medicine,” Dr. Natale continued. “Not simply taking a chemotherapy cocktail off the shelf and giving it to everybody with lung cancer, but analyzing their tumor, finding precisely what’s driving the growth or that’s blocking the immune system from attacking the cancer, and using that information to give the patient a specific treatment that is much more likely to be successful, much more likely to help them.”

How, Exactly, Does Keytruda Work?

Keytruda falls into a class of drugs called checkpoint inhibitors, which allow the body’s immune system to fight off its own cancer by blocking a problematic “don’t attack me” signal on the cancer cell.

Melanoma and lung cancer were the first two major indications to receive approval for checkpoint inhibitors, but clinical trials have suggested it could be helpful across many other cancers.

"I have patients where the immune system has cleaned out the cancer, and they remain cancer-free," Dr. Geoffrey Oxnard, a thoracic oncologist at Dana-Farber Cancer Institute told SurvivorNet, explaining that the reason that the body's immune system doesn't naturally attack cancer on its own has to do with markers found on cancer cells. These markers, such as PD-L1, bind with other markers found on immune T cells (in PD-L1's case, that marker is PD-1) to create signals telling the immune system not to attack. A similar response happens with the protein B7, which binds with the CTLA-4 marker.

"It's a Jedi mind trick that tells the immune system 'move on by ignoring me,'" Dr. Oxnard explained. "If we block that signal, the immune system wakes up, sees the cancer, and attacks."

Checkpoint inhibitors do exactly that: they block the "don't attack" signal.

Now, as the new analysis shows, the group of patients with lung cancer who are able to benefit from this revolutionary drug is continuing to expand.

Dr. Geoffrey Oxnard spoke with SurvivorNet about the importance of genetic testing for late-stage lung cancers

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Caroline Hopkins is a writer for SurvivorNet. Read More