For Lung Cancer Patients With The EGFR Mutation: The Benefit of The Drug TAGRISSO Plus Chemotherapy

For lung cancer patients with an EGFR mutation, “TAGRISSO is the best drug in the metastatic setting,” Dr. Roy Herbst, told SurvivorNet. Dr. Herbst is a nationally recognized lung cancer researcher who serves as deputy director and chief of medical oncology at Yale Cancer Center and Smilow Cancer Hospital. He sees some potential benefit in the data from the recent study, “The time of progression is longer and the primary endpoint of the trial was met.” With that being said, he remains skeptical about whether the combination therapy will have a long-term benefit on this patient population. In baseball terms he says: “I think it’s a single or a double. It’s not a home run at all.”

Arun Krishna, the US Commercial Lead for Lung Cancer at AstraZeneca says this recent announcement provides a new potentially beneficial alternative for many of those who are already qualified for TAGRISSO alone: “Patients with a positive EGFR mutation, they always had an option for TAGRISSO as a monotherapy. This was approved more than five years ago.” Krishna told SurvivorNet, “In the US this is now a new option, which is a combination of TAGRISSO plus chemotherapy showing benefit for patients in the metastatic stage. So these are patients who’ve been diagnosed with either locally advanced, which are Stage 3B-3C or Stage 4 disease.”

There is a lot of information to unpack in this announcement. What does this all mean? How does this information impact my lung cancer? Here we break down these terms and answer common questions you may have.

What are locally advanced and metastatic lung cancer?

Lung cancer can present at any stage with the treatment options differing based on the specific stage of the lung cancer. The stage of a cancer essentially describes how large that cancer is and how much it has spread. Early stage cancers are typically smaller and have not spread to other sites outside the lung. Locally advanced stage lung cancers are often larger and more invasive with more lymph nodes involved, while metastatic lung cancer has spread distantly. When lung cancer spreads it can go to several sites outside of the lung, most commonly to bones and the brain.

What does it mean to have EGFR-mutated lung cancer?

In addition to the lung cancer stage, doctors look at the cancer cells themselves by doing something called molecular testing on your tumor biopsy or using a blood sample. The test results can determine additional information about the makeup of your cancer, which is used to make treatment decisions. The type of mutation can vary depending on the cancer type. In lung cancer a common DNA mutation is epidermal growth factor receptor, or EGFR.

EGFR is like a switch on the cell that when activated tells the cell to grow. When EGFR mutates it is constantly turned on, which means the cell grows too much. This can result in cancer growth. If your lung cancer has a mutation in EGFR, it is called an EGFR-mutated lung cancer or EGFR-positive lung cancer, which is a specific subtype. This can affect treatment options and also tells us how the cancer typically behaves.

How common is EGFR-mutated lung cancer?

The rate of EGFR-mutated lung cancer can vary depending on the population, but it typically comprises 15-20% of North American and European patients. It can be almost 50% in Asian populations.

What is the current standard of care for advanced EGFR-mutated lung cancer?

If you have metastatic lung cancer which has spread to distant sites outside the lung, your healthcare team will use information from your biopsy to individualize the therapy. If your lung cancer is EGFR-mutated, osimertinib is typically recommended as the first treatment. This medication is also known as TAGRISSO. 

TAGRISSO is often used as a monotherapy, meaning that it is used by itself with no other medications. Other local treatments like surgery or radiation can be added in as needed if you are having local problems like bone pain.

A recent study, in which Yale’s Dr. Herbst was the lead author, showed that it worked very well for early-stage non-small cell lung cancer (NSCLC) patients too.

His study, which released its results at ASCO in 2023, showed that TAGRISSO demonstrated an overwhelming improvement in the treatment outcomes for early-stage NSCLC patients with EGFR mutations who had their tumors removed, reducing their risk of death by 51%.

Another Treatment Option For Patients With The EGFR Mutation

In early September 2023, AstraZeneca announced the results for their Flaura 2 Phase III trial, where they took their blockbuster TAGRISSO drug and added chemotherapy. Their results showed that in patients that have locally advanced or metastatic EGFR-mutated lung cancer and have not received any previous medication to treat the lung cancer, when chemotherapy is used in combination with TAGRISSO, the progression-free survival is nine months longer than using TAGRISSO alone. This shows a decrease of disease progression and death by 38%.

Krishna of AstraZeneca explained TAGRISSO as a monotherapy remained a great option for most EGFR-mutated lung cancer patients.

“This is just another option for certain patients where they would like to include chemotherapy along with TAGRISSO and potentially focused on patients who could be slightly so-called sicker patients,” Krishna says.

“So for example, patients with CNS metastasis, metastasis in the brain. Patients with certain types of mutation like L858R, we’ve seen that there’s a significant improvement for those types of patients.”

Lung cancer specialists with whom SurvivorNet spoke, seem to back up this view.

What is progression-free survival (PFS)?

Progression-free survival (PFS) is an all-encompassing term that tells you how long after a treatment someone goes without progression of the disease or death from any cause. So the longer a PFS is the longer a patient goes without growth of the primary tumor or distant disease, appearance of new metastatic disease, or death. If you have a longer time without progression of disease this means you can potentially go a longer period of time without additional treatment or the need to change therapy.

Are there any other interesting results from the announcement?

“In particular, in the group of patients with cancer having spread to the brain, this prolongation was even more pronounced,” Dr. Balazs Halmos, medical oncologist and director of the Thoracic Oncology Program at Montefiore Medical Center, tells SurvivorNet. So in patients with EGFR-mutated lung cancer which has spread to the brain, the PFS is even better with chemotherapy plus TAGRISSO vs. TAGRISSO alone.

When cancer has spread to the brain it can be very debilitating and cause significant problems. So with an even better PFS and the fact that cancer in the brain can have a huge impact on people’s lives, according to Dr. Halmos, “these results at least warrant considering Osimertinib+ chemotherapy as an option to consider.”

Is the AstraZeneca announcement surprising? Does an improvement in PFS matter?

“An improvement in progression-free survival of course was a given for this study. If we combine two of the most effective treatments, of course we achieve better and more durable remissions,” says Dr. Halmos.

As Dr. Halmos explained, both TAGRISSO and traditional chemotherapy are known to be effective for EGFR-mutated cancer. If you use two effective treatments you are going to get a better response to treatment and the cancer is going to take longer to come back. So an improvement in PFS is not surprising. With that being said, the use of more medication also comes with increased toxicity and side effects. Dr. Halmos was impressed by the study results but still remains skeptical.

“Will the combination work better than just using one after the other? Will the added side effects of chemotherapy pay dividends so that 2+2 could equal 5? From this angle of course the ultimate question is that of overall survival,” Dr. Halmos says.

What this means is that improved PFS is always encouraging to see, however it is not the most important factor. The longer you can go without the disease progressing is important. But the most important result to see is an improvement in overall survival. Does this combination of chemotherapy and TAGRISSO compared to TAGRISSO alone prolong your life? Although 9 months improvement in PFS is promising, at this point it is too soon to tell if overall survival is improved.

Dr. Herbst also believes there is something else worth considering when thinking about doing a TAGRISSO-chemo combination therapy — the sacrifice you may need to make to go into a hospital or infusion center to get treatment versus just being able to take TAGRISSO , an oral agent or pill, from home. That could make a big impact on the quality of your day-to-day life.

“If someone has EGFR mutated disease, they get the oral agents (TAGRISSO). They come back every couple of months. They don’t have to keep coming in. Coming in for an infusion, you get the IV, you have to wait your whole morning. It prevents you from traveling. It ties you down.”

Like Dr. Halmos, Dr. Herbst is not sure whether he would recommend the combination therapy to his patients just yet, until he sees how it impacts overall survival:

“I don’t think it’s going to take off right away. I think they’re going to wait a little bit and only use it in certain patients and we’ll wait for the (overall) survival.”

How does this affect my treatment?

The information gathered from this study and reported by AstraZeneca is important information to consider. The results will not change the standard-of-care, or nationally recommended guidelines, at this time. However, as the study continues and patients are followed for longer periods of time, there might be a significant improvement in the overall survival at which point combination chemotherapy and TAGRISSO might be more widely used. Again, this will take time to determine.

As described above, this combination therapy of chemotherapy and TAGRISSO could be considered on an individual basis where it is vital to prevent progression of disease and accept a higher rate of side effects. This means specifically patients with involvement of the brain and central nervous system.

If you have additional questions about TAGRISSO and combination chemotherapy, please don’t hesitate to bring it up with your health care team.

What are the next steps?

As the study continues and the data matures with patients being followed for longer periods of time, information regarding overall survival and progression-free survival will continue to develop. Depending on those results, current recommendations for first-line treatment could change.

Learn more about SurvivorNet's rigorous medical review process.

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