Treatment Information

Know your treatment options

Each cancer story is personal. Treatment should be personal too. Your healthcare team will recommend treatment options specifically for you. Options may include chemotherapy, targeted therapy, immunotherapy, radiation, or surgery. Learn more about current treatment options from our treatment update at the 2021 Advocacy Summit by watching the video.

Comprehensive Biomarker Testing and Targeted Therapies

Comprehensive biomarker testing is a way for doctors to test the genetic makeup of a tumor and to help make the best decision possible about your treatment. The more that is known about the tumor determines how specific and targeted your treatment options can be.

About Comprehensive Biomarker Testing

Who should be tested?
Every patient with stage IV non-squamous lung cancer should be tested. Testing should be discussed for stage I-III disease as well, because in the case of one particular change, EGFR, there is approved adjuvant therapy.
How is testing done?
Traditionally, all testing is done on a piece of cancer—a biopsy or surgical specimen. However, mutations can also be tested on tumor-derived DNA found in blood. Regardless of whether cancer DNA is obtained from tumor or from blood, there are different ways that it can be tested in the lab. Traditionally, the doctor ordered testing individually for each mutation he or she was interested in. Many centers are moving towards a method called next generation sequencing which would test for all of the above mutations in one test. The most sensitive and comprehensive next generation sequencing includes an “RNA fusion panel;” commercially, this is available through Foundation Medicine (the poorly named “heme” test), Tempus and Carris.
When should you get tested?
Your tumor may have been tested with your initial biopsy. However, if not enough tissue was collected biomarker testing can be done at any time. In many situations, patients with known mutations whose cancer grows on targeted therapy can benefit from being tested again.
Where can you get tested?
Most major medical centers often offer biomarker testing. Talk to your doctor to discuss getting tested.

Facts about DNA Mutations

Every living thing is made up of building blocks called cells. Inside of each cell is a set of instructions for how to do its job. These instructions are called DNA and mistakes in them are called mutations. Mutations can be inherited (rarely in lung cancer), occur due to carcinogens (cancer-causing chemicals such as those found in cigarette smoke) or through bad luck. Regardless, they can cause the cell to forget how to do its job and instead learn how to make copies of itself, spread and grow. A cell with such mutations is called a cancer cell.

In non-squamous (mostly adenocarcinoma) of the lung, we can identify the specific changes that happened early in the process of the once-healthy cell becoming cancerous. These events are called, “driver mutations.”

Some of these mutations have drugs that can target them. Targeted therapies mostly only work when matched to target. When tried in patients without the change that the targeted therapy actions, they tend to fail. But, when properly matched, these drugs tend to work better than chemotherapy. More specifically, their advantages are:

They work better: Response rate is arbitrarily defined as 30 percent shrinkage of cancer (it needed to be set somewhere to allow drugs to be compared to each other, but a patient with 29 percent shrinkage of cancer and a patient with 31 percent shrinkage of cancer really derive similar benefit, even if one is labeled as having “partial response” and the other as, “stable disease”). The response rate with targeted therapies is at least 66 percent and most of the remaining 1/3 of patients derive benefit less than 30 percent shrinkage. They also tend to control cancer longer than chemotherapy.

They’re less toxic: Targeted therapies are not side effect or risk free. But, they do tend to have a lot fewer side effects than chemotherapy. Side effects vary by agent, but rash and diarrhea are particularly common with these agents.

They’re more convenient: While most chemotherapy is IV, most targeted therapies are oral.

With that in mind, let’s talk about some important mutations:

EGFR:

EGFR is present in about 15 percent of adenocarcinoma. Guidelines say that any patient with adenocarcinoma should be tested for EGFR, but statistically, the mutation is more common in nonsmokers, women and Asians. The standard treatment of EGFR in the US and much of the world is the third generation inhibitor Osimertinib. PFS (time until cancer growth or death) is about 19 months when used as first anticancer therapy. The combination of the 1st generation inhibitor, erlotinib, and the IV VEGF agent bevacizumab is also approved for first line treatment.

ALK:

EML4/ALKis a rearranged gene that is found in about 4 percent of adenocarcinoma of the lung.  The development of ALK inhibitors for patients whose cancer is driven by this change is inspiring; it was the fastest time from scientific discovery of target to FDA-approved drug ever. The most commonly used first line drug against ALK alectinib after which lorlatinib and brigatinib are considered.

ROS1:

ROS1 is another rearranged gene with a lot of biologic similarity to ALK. It is present in about 4 percent of adenocarcinoma of the lung and is treatable with the targeted therapies crizotinib (same one as for ALK) or Entrectinib. Multiple new ROS1-targeted agents are in clinical trials; repotrectinib is likely to be the next one approved.

MET:

Both high level amplification of MET (duplication of the DNA instructions) and a specific mutation called MET del 14 can drive adenocarcinoma of the lung. Both are actionable with capmatinib or tepotinib. MET is often missed with DNA-only NGS, so an RNA fusion panel is important to find it.

RET:

RET is gene re-arrangement driving about 2 percent of adenocarcinoma of the lung and also present in a number of other cancers.  Selpercatinib and pralsetinib were recently approved for the treatment of RET NSCLC.

NTRK:

NTRK is a rare gene rearrangement (<1 percent of NSCLC).  It is often missed with DNA-only NGS, so an RNA fusion panel is important to find it.  It can be actioned with larotectinib or entrectinib.

BRAF:

There are many kinds of BRAF mutations. About half are V600E and these are the ones that are actionable with targeted therapy. Single-agent BRAF inhibitors (vemurafenib, dabrafenib) are active but double-inhibition with the combination of a BRAF inhibitor and a MEK inhibitor works better (dabrafenib plus trametinib).

kRAS:

kRAS has been known to be mutated in human cancers since about the dawn of the internet, yet we still have no approved kRAS directed therapies. That is likely to change soon. Sotorasib and adagrasib are likely to be approved in 2021 for kRAS G12C, which is about 13 percent of adenocarcinoma of the lung.

HER2:

HER2 is mutated in about 2 percent of adenocarcinoma of the lung.  Multiple drugs may be considered off label for it (such as TDxD) and multiple drugs are in late stage development for it and likely to be approved in the near future.

Bridging the Comprehensive Biomarker Gaps

New biomarkers are being discovered at a rapid pace, unlocking new breakthrough treatments for patients and their families. Unfortunately, many patients still don’t get the biomarker testing they need, especially in North Carolina, where utilization of this important tool remains low.

That’s why the Lung Cancer Initiative of North Carolina is proud to join Lilly in a new campaign to expand access to comprehensive biomarker testing and give patients and providers clinically actionable information to inform their course of treatment.

Additional Resources