Targeted therapy for non-small cell lung cancer (NSCLC) is like “targeting” a tumor by targeting the “bull’s eye. The “bullseye” is a specific gene variant, such as EGFR, ALK, and ROS1.
So, if genetic testing identifies a mutation, do we just need to take the target drug that corresponds to the “bullseye” alone? Is it better to combine it with other therapies? This article is an attempt to explain.
Targeted drugs alone are the norm
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Multiple international multicenter clinical studies to date have demonstrated the efficacy and safety of targeted agents in patients with NSCLC positive for three genetic variants: EGFR mutations, ALK rearrangements, and ROS1 fusions, who live 2 to 3 times longer.
The first-line use of these drugs alone has been recommended in both national and international clinical guidelines, and is an excellent choice for patients with these three driver-positive genes. If disease progresses after first-line therapy, there are now second- or third-generation drugs approved for second-line therapy for the three gene mutations mentioned above. For example, if a patient with an EGFR gene mutation progresses and then has genetic testing and is found to have a T790M mutation, then a third-generation EGFR inhibitor is the first choice.
We used the EGFR mutation as an example of what happens with targeted agents alone. Maybe you already had brain metastases when your lung cancer was first detected. Several studies have shown that EGFR-TKI (EGFR tyrosine kinase inhibitors) class of targeted agents have shown good efficacy in patients with advanced EGFR mutation-positive, brain metastases, with intracranial efficiencies up to 70% or more.
At this point, whether you also need to add radiation therapy will depend on the severity of your specific symptoms, the site of the metastases, and other different circumstances, and you should first talk fully with your supervising physician. In most cases, simple monotherapy is sufficient to achieve a satisfactory outcome.
Can targeted drugs be used in combination with other treatments?
There are still questions about whether and when targeted therapies can be used in combination with other systemic therapies such as anti-angiogenic therapy, chemotherapy, and even other targeted drugs. Most combination regimens are still in the clinical research phase.
Still using EGFR mutations as a few examples:
- Combination with anti-angiogenic therapy: Some previous international studies have reported that in patients with positive EGFR mutations, the combination of EGFR-TKI analogs with anti-angiogenic therapy prolonged progression-free survival by about six months compared with the group on its own.
- Combination with other targeted agents: In some clinical studies, EGFR-TKI analogs in combination with other targeted agents, such as C-MET inhibitors, have also shown some efficacy in patients with EGFR mutations and concomitant C-MET overexpression/amplification.
- Postoperative adjuvant: Targeted therapies have also shown promising efficacy as postoperative adjuvant therapy in patients with locally advanced EGFR mutation-positive lung cancer.
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Again, we remind you that most of the “strong combination” regimens are still in the research phase. In our lung cancer guidelines, the combination of targeted therapy with chemotherapy is an “optional strategy” (Class 2A evidence, i.e., insufficient evidence from studies but uniform expert understanding) and is not recommended in combination with other therapies, whereas targeted drug monotherapy is the basic strategy and is supported by the highest level of evidence. In clinical practice, combinations of targeted agents with other therapies are also rarely recommended for first-line treatment.
As for dosing regimens, please be sure to visit your oncology specialist and have your doctor evaluate whether to consider relevant clinical studies or dosing regimens based on your individual genetic status.
Conclusion
Patients with advanced NSCLC who have a mutated “bull’s-eye” are appropriate for targeted therapy, and it should be used in the first line as early as possible. When you see a “positive” genetic report for EGFR, ALK, ROS1, etc., you should go to an oncology clinic and seek help from your doctor.
Targeted agents alone are the norm. The combination of local therapy, such as radiotherapy, or systemic therapy, such as anti-angiogenesis or chemotherapy, requires a definitive consultation with your oncologist.
Today we have entered the era of “individualized” oncology care. Each patient is unique. Treating each patient individually will provide the greatest benefit to you.
Co-authors: Dr. Bai Xiaoyan Dr. Zhang Yichen Dr. Zheng Meimei, Guangdong Provincial People’s Hospital, Guangdong Lung Cancer Institute