Many patients will encounter two common “old friends” in their lives with lung cancer: targeted therapy and chemotherapy. As science advances, a judicious combination of targeted agents and chemotherapy will maximize your survival benefit. In this article, we’ll take a look at what “rational combination” means.
Targeted therapies – use only if there is a “target”
Targeted drugs are a class of small-molecule, orally administered drugs that target specific genetic mutations that drive tumorigenesis and progression. Currently, only patients with non-small cell lung cancer (NSCLC), especially lung adenocarcinoma, can be treated with targeted therapies.
To date, the two main categories of mutations that are commonly available with targeted agents are EGFR gene mutations and ALK/ROS1 fusion genes. Drugs targeting the former, such as the familiar gefitinib (trade names like Eressa) and erlotinib (trade names like Troche), and drugs targeting the latter, such as crizotinib (trade names like Securitas).
Therefore, targeted therapy is preceded by genetic testing to confirm the presence of a treatable target. You have to choose a targeted drug only if you have a target, otherwise you need to consider other treatments.
Targeted therapy is more effective than conventional chemotherapy for patients with the appropriate target. The landmark study in this area is the IPASS study, a large multicenter clinical study initiated by Chinese investigators. It confirmed that the targeted agent gefitinib is more effective and has fewer side effects than chemotherapy in patients with advanced NSCLC (mainly non-smoking or oligometastatic lung adenocarcinoma) who have EGFR-sensitive mutations.
Subsequently, more than a dozen other studies, both here and abroad, have confirmed that targeted agents are more effective and have less adverse effects in patients with well-defined targets.
In addition to EGFR, there are drugs that target other targets in the clinic, such as ALK and ROS1, and although the incidence of mutations in these targets is relatively low in the population, there are only two possibilities for you as an individual, so testing is essential. Asian non-smoking women, in particular, are more likely to have driver gene-positive lung cancer.
As scientific research advances, more and more therapeutic targets will be identified and targeted drugs will be available in the future.
In summary, when you are diagnosed with advanced lung cancer, pathology and genetic testing should be performed first after obtaining a biopsy of the tumor tissue. Patients who have a clear therapeutic target (mutation) are suitable for targeted therapy. For patients without a target, “blind” testing is wrong and will only delay the disease and increase adverse effects.
What to do if you don’t have a “target”-chemotherapy is an option
Many patients have a fear of talking about chemotherapy. In fact, when your genetic testing shows no targetable genetic variants, chemotherapy is often just as effective in controlling the tumor.
For patients with advanced NSCLC without sensitive mutations, chemotherapy is a more reasonable initial treatment choice than “blind” targeted drugs, and there is more research data to support this.
In addition, if you are resistant to a targeted drug after a period of time and no more mutations are found that can be targeted, you will also need chemotherapy to manage your disease.
As science advances, chemotherapy drugs are also evolving rapidly today: pemetrexed, gemcitabine, albumin paclitaxel, and other drugs are blooming. The side effects of these new chemotherapy drugs are greatly reduced. You will need to talk fully with your primary care physician to develop an exclusive treatment plan based on your type of pathology, past drug history, liver and kidney function, etc.
If you experience adverse effects such as nausea or hematocrit, do not panic and talk to your doctor promptly. Your doctor will tailor your regimen, adjust or reduce the dosage, and take countermeasures for adverse reactions, which usually do not affect treatment or efficacy.
Of course, some patients without driver mutations may also have access to immunotherapy. Immunotherapy is evolving rapidly, with two new drugs for immunotherapy (nabolutumab and pablizumab) already available in China and more in clinical trials. You can consult with your doctor to discuss whether you might consider this option. But again, immunotherapy is not perfect, and it can only benefit “some” patients.
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Co-reviewed by: Guangdong Provincial People’s Hospital Guangdong Lung Cancer Institute Director Zhou Qing Dr. Bai Xiaoyan Dr. Zhang Yichen