This year, 127,000 Americans will die of lung cancer, making it the most deadly cancer by far and the second leading cause of death in the United States. (Cardiovascular disease is the first.) But if you or a loved one is diagnosed with lung cancer this year, don’t despair. Medical breakthroughs are dramatically extending the lives of patients with lung cancer—particularly people with non-small cell lung cancer (NSCLC), which accounts for 85 percent of all lung cancers.

Two classes of new drugs have proven themselves very effective at extending life.

  • Checkpoint inhibitors. These immunotherapy drugs (also called monoclonal antibodies) energize the immune system to kill cancer cells by blocking one of two cancer-encouraging proteins, PD-1 or PDL-1. These drugs include pembrolizumab (Keytruda), nivolumab (Opdivo), and ipilimumab (Yervoy). They are now often used as first-line therapy before or with chemotherapy.
  • Targeted therapy. These drugs turn off one of several genetic mutations (oncogenes) that can drive NSCLC, like EGFR, EML4-ALK, ROS1, and KRAS. About 50 percent of NSCLC patients have a “targetable” mutation. These drugs include crizotinib (Xalkori), osimertinib (Tagriso), and alectinib (Alecensa). They’re very effective.

The average survival time in lung cancer that has metastasized (spread beyond the lungs, typically to the brain, bones, or liver) is 12 to 14 months after treatment. But 70 to 80 percent of metastatic NSCLC patients who have the ALK-positive mutation respond to crizotinib (Xalkori) or similar drugs. Among them, 62 percent are alive five years later.

Another breakthrough: If a patient becomes resistant to a gene-­modulating drug—which commonly happens within a year—there are now second- and third-generation drugs.

In one of the latest scientific papers on targeted therapy—published in the Journal of Clinical Oncology, researchers from across the world studied 682 patients with NCSLC and the EGFR mutation who’d had their tumors surgically removed. Investigators divided the patients into two groups: One group received osimertinib and the other received a placebo. Over four years, 73 percent of the patients taking osimertinib had disease-free survival, compared with 38 percent in the placebo group. Among the placebo group, 60 percent had a recurrence of lung cancer, compared with 27 percent in the osimertinib group. The osimertinib group also had fewer metastases.

Drugs for KRAS mutation

A new development in gene-­modulating medications is a class of drugs that target the KRAS G12C genetic mutation. This is the most common, smoking-linked genetic mutation in NSCLC, occurring in 12 to 15 percent of people with the disease. (Never-smokers can also have this mutation.) Until recently, there have been no gene-modulating medications for this form of the disease.

On May 28, 2021, the FDA approved sotorasib (Lumakras) for KRAS G12C-mutated NSCLC that is either locally advanced (spread into nearby tissues or lymph nodes) or metastatic (spread beyond the lungs). The drug was approved for people who already had one type of systemic therapy, like chemotherapy or hormonal therapy.

In December 2022, the FDA approved adagrasib (Krazati) for KRAS G12C-mutated NSCLC for any case of locally advanced or metastatic cancer.

Genetic testing

Unfortunately, only 50 to 60 percent of patients who are newly diagnosed with NSCLC receive genetic testing to see if they are a candidate for a gene-­modulating drug. But among those tested, about half are candidates.

The testing is FDA-approved, and Medicare and most other insurance cover both the testing and the gene-modulating drugs. So, why is there such a low rate of testing for a gold standard therapy?

There is a disconnect between the scientific findings on these newer classes of cancer drugs and routine care in community, nonacademic cancer centers. 

Bottom line: If you’re diagnosed with NSCLC, testing for your mutation status is a must to ensure the most effective treatment. Talk to your oncologist about your options.

If you don’t have a genetic mutation, then you should be offered immunotherapy, along with surgery and/or chemotherapy. About 40 percent of patients who do not have a genetic mutation respond to immunotherapy. Talk to your oncologist about this approach.

Early diagnosis

The majority of people who develop lung cancer are smokers or former smokers. About 10 to 20 percent of cases occur in never-smokers. The best way to detect their cancer early is with low-dose computed tomography (LDCT) screening, conducted yearly.

In March 2021, the U.S. Preventive Service Task Force revised the screening guidelines to recommend annual LDCT screening for people who meet the following criteria:

  • Adults ages 50 to 80
  • A 20 pack-year smoking history (one pack a day for 20 years, or one-half pack a day for 40 years)
  • Current smokers or those who have quit within the past 15 years.

If you meet these criteria, talk to your primary care physician about getting a yearly LDCT for your lungs. This screening is crucial to your longevity because the earlier lung cancer is detected, the greater the likelihood you can successfully fight the disease.

Liquid Biopsy

Anyone with suspected lung cancer should receive a biopsy before starting therapy. In many cases, however, a tissue biopsy isn’t possible. That’s where a liquid biopsy comes in.

This blood test, which was approved by the FDA in 2016, is as accurate as a tissue biopsy, and it can be routinely used where a tissue biopsy is not an option.

A five-year study published in the March 2023 issue of Clinical Lung Cancer showed that a liquid biopsy is, in many ways, superior to tissue biopsy. Results came back 26 days sooner. The liquid biopsy was more accurate than the tissue biopsy in identifying biomarkers for treatment—76 percent of the time for liquid, 55 percent for tissue. And there was no difference in treatment outcome, progression-free survival (the length of time after receiving treatment when the disease does not progress), or overall survival (the time between receiving treatment and death).

If it’s time for a biopsy, talk to your oncologist about this option.

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