An Overview of First-Line Treatment for Cancer

First-line treatment or therapy simply refers to the initial, or first treatment recommended for a disease or illness. This may also be referred to as primary treatment, initial treatment, or induction therapy. With many conditions, including cancer, there are many possible treatments that could be effective. First-line treatment is the one that, for most people, is expected to provide the best results with the fewest number of side effects. In contrast, second-line treatments are used when the first-line treatment failed to improve a cancer, or if it worked for a while and then the cancer progressed, and tend to be less effective.

First-line treatments change all of the time with cancer. As newer studies find better options, whether it involves surgery, radiation therapy, targeted therapy, or immunotherapy, the "first-line" treatment recommendations for a disease are continually changing. For example, with some advanced non-small cell lung cancers (without mutations that can be targeted), chemotherapy was once considered the accepted first-line treatment by oncologists, but a 2018 study explains how Keytruda (pembrolizumab) is used with chemotherapy in this setting.

First-Line Treatment for Cancer - Illustration by Ellen Lindner

Verywell / Ellen Lindner

Understanding First-Line Treatment

First-line treatment is usually the standard treatment (the "gold standard") given when someone is diagnosed with a particular disease or condition, such as lung cancer. In other words, it is likely the treatment most oncologists would first choose in treating someone. That said, there are no general "rules" stating which treatment has to absolutely come first, and in addition to that, it's important to work with your oncologist to choose the treatment that is best for you as an individual. Only you can be your own advocate and select the treatments which offer you the best outcome while minimizing the side effects you are willing to tolerate.

With regard to cancer, first-line treatment may actually be a combination of treatments, such as surgery, chemotherapy, and radiation therapy, given in succession. Therefore, a better term would probably be "first-line treatment regimen or protocol." Neoadjuvant therapy, chemotherapy given before surgery to reduce the size of a tumor, or adjuvant therapy, given after surgery to reduce the risk of recurrence, are considered components of first-line therapy in this setting.

First-Line vs. Second-Line Treatment

In contrast to first-line treatment, second-line treatment is usually a treatment which is chosen after first-line treatment has failed to achieve the goal (either it doesn't work or all, or it works for a period of time and then stops working), or has side effects requiring you to stop using that treatment. Second-line treatments are often inferior to first-line treatments but not always. For example, with metastatic breast cancer, second-line therapy tends not to control the cancer for as long a period of time as first-line therapy. In some cases, there are two treatments (or more) that may offer very similar results (and have similar side effects), and second-line treatment may be equally effective to first-line therapy.

Third-Line Therapy and More

In addition to first- and second-line treatments, there are often further options. For example, with metastatic breast cancer, you might hear your oncologist talk about fourth-line or fifth-line therapy. This therapy might be tried when first-, second-, and third-line treatments are no longer working to control cancer.

It Can Vary for the Same Cancer

Every cancer is different, and it is important to keep this in mind if you hear about another treatment for your type of cancer. First-line treatment for one cancer of a particular type and stage may be different than the first-line treatment of another person's cancer of the same type and stage but a different molecular profile. In addition to this, other factors such as age, general health, and co-existing conditions may make what is a first-line treatment for one person a second-line therapy for another.

First-Line Treatment Is a Choice

We are entering an era known as "participatory medicine" in which people with cancer are much more involved in their health care. Decisions are made as a team, rather than the paternalistic relationship between healthcare providers and patients of the past. After a discussion, and learning as much as you can about your cancer, you will likely have a choice between different approaches.

Questions to Ask 

When you and your healthcare provider consider a first-line treatment or first-line treatments, think through these questions.

  • Clarify the type and stage and molecular profile of your tumor. Is there any further testing that should be done? (If you've been diagnosed with advanced cancer, ask about the molecular profile of your tumor, and if this hasn't been done, ask why not).
  • What is your goal in receiving this treatment? Different people have different goals. Some people wish to be as aggressive as possible (and tolerate whatever side effects may occur) for a chance to extend life, whereas others may opt for fewer side effects and better quality of life even if survival may be shorter.
  • What side effects are you willing to tolerate? The side effects people are willing to tolerate can vary tremendously. Some people wish to avoid skin rashes whereas others find fatigue to be the worst symptom. Some people may wish to avoid nausea at all cost, whereas others wouldn't mind experiencing some nausea if their fatigue would be milder.
  • What is a second-line treatment if this treatment doesn't work? How about third-line, fourth-line, and more? Some people find it very helpful in coping to know what the next steps might be if their current treatment does not work.
  • Are there any clinical trials available that may better suit your needs? Ask about these, or research these right away, as some first-line treatments may disqualify you from some clinical studies. If you are considering a clinical trial but would like to try a different treatment first, ask if the treatment you are considering might disqualify you from that clinical trial down the road.
  • What is the cost of the treatment(s)?
  • What is the average success rate of the treatment(s)?
  • What are some possible risks?
  • How soon will you need to begin treatment?
  • Where would your healthcare provider recommend you have a second opinion?

Alternative and Complementary Treatments

It's important when talking about treatment to clarify what is meant by "alternative treatments." Most people now use the phrase alternative treatments to refer to complementary treatments that are offered by some cancer centers. In this setting, therapies such as acupuncture, meditation, massage, and yoga are used in an integrative fashion—that is, they are used along with traditional treatments such as chemotherapy. These complementary treatments may help some people cope with the side effects of cancer and cancer treatments.

There has been some interest (and many internet scams) with alternative approaches that substitute another treatment for conventional treatments. These are dangerous, and there are currently no alternative treatments that would be considered a first-line treatment for cancer.

A Word From Verywell

First-line treatments are those which you and oncologist will choose as the best first choice for your particular cancer. There are often several different options available, yet first-line treatments are those which are most expected to control your disease with the fewest side effects in the process. Whether second-line therapies with your cancer are inferior, or instead interchangeable, with first-line therapy will depend on many different factors. Take time to learn about your cancer so you can make an educated choice on which therapies should be the first-line treatments for you. 

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  • American Society of Clinical Oncology. Cancer.Net. What If the First Treatment Doesn’t Work?

  • Ninomiya K, Hotta K. Pembrolizumab for the first-line treatment of non-small cell lung cancer. Expert Opinion on Biological Therapy. 2018;18(10):1015-21.

By Lynne Eldridge, MD
 Lynne Eldrige, MD, is a lung cancer physician, patient advocate, and award-winning author of "Avoiding Cancer One Day at a Time."