Lung cancer is one of the toughest cancers to treat — and with tough treatment come some truly debilitating side effects, such as nerve damage, loss of appetite, severe nausea and vomiting, diarrhea or constipation, hair loss and mouth sores.
That’s because typical lung cancer treatment is a bombardment with a combination of different types of chemotherapy drugs (usually Cisplatin or Carboplatin) that attack not just cancer cells, but other, healthy cells — such as those in the bone marrow (where new blood cells are made), the lining of the mouth and intestines, and the hair follicles.
These drugs also cause blood counts to fluctuate and platelets to plummet, leading to an increased risk of infection, bruising or bleeding, and severe fatigue.
It’s a blunt approach, but until recently it was the only weapon in cancer doctors’ arsenals. However, the promising frontier of targeted lung cancer treatment may provide fresh hope. “Ultimately what we need to do to improve cancer treatment is create drugs that just target the ‘abnormal machinery’ in the body,” says Jeremiah Martin, MD, assistant professor of thoracic surgery and surgical director of the Markey Multidisciplinary Lung Cancer Clinic at the University of Kentucky, Lexington.
Targeted Lung Cancer Treatment
Essentially, targeted treatment is just what it sounds like — zeroing in on the cancer and bypassing healthy tissue. Typically administered by pill, this form of treatment is matched to a cancer’s specific gene mutations, proteins, or the tissue that is contributing to cancer growth. The aim of targeted treatment is to block the growth and spread of cancer cells.
Not all lung cancers can be treated this way yet. The key to targeted cancer treatment are biomarkers, proteins or molecules in the tumor that give doctors a more detailed picture of the lung-cancer tumor, and thus a more targeted approach to attack it. Biomarkers are found on the surface of the cells, or in the genes that program cells. Biomarkers that science has targeted treatments for include:
- Epidermal growth factor receptor (EGFR)
- Anaplastic lymphoma kinase (ALK)
- K-ras mutations (KRAS 1)
When a person is diagnosed with lung cancer, doctors may perform tests to determine if one of these biomarkers is present in the tumor.
How Well Does Targeted Therapy Work?
In a study conducted last year at Wake Forest University and published in the Journal of the American Medical Association, testing lung cancer tumors for genetic variations helped yield targeted drug treatments that were more successful (patients lived longer)
Is targeted treatment as effective as traditional treatment? It seems so – A study showed that testing lung cancer tumors for genetic variations helped yield drug treatments that were more successful (patients lived longer) than those who didn’t receive such targeted therapy.
Additionally, researchers at Memorial Sloan Kettering Cancer Center using data from the Lung Cancer Mutation Consortium (a study that ran from 2009-2012 and examined genetic drivers in the tumors of 1,007 lung cancer patients), found that 64% of tumors had a genetic mutation. Patients with the genetic mutation who received targeted therapy had a median survival rate of 3.5 years (compared to 2.4 years for patients who received no targeted therapy). Those whose tumors had no genetic mutation had a 2.1 year survival rate.
‘Patients might only be getting an extra year, but it’s an extra year not spent in hospital.’ — Jeremiah Martin, MD
It’s not surprising that genetic testing of tumors is proving more effective than other treatments we’ve seen to date. “Cancer is a disease of a patient’s genes,” says Craig Stevens, MD, PhD, radiation oncology chief at Beaumont Hospital, Royal Oak and Radiation Oncology chair for the Oakland University William Beaumont School of Medicine. “Sometimes that disease is inherited, and sometimes those cells acquire mutations over time, via environmental changes like smoking, or just randomly. The way these drugs work is to have the ability to target those particularly abnormalities that are present in the cancer and turn them off — without impacting the healthy cells.”
So what targeted therapies have proven to be the most effective for which mutations? “EGFR inhibitors are the first drugs that have really been shown to work, for patients with the ALK or EGFR mutations,” says Dr. Stevens. These patients, he says, typically have non-small-cell lung cancer (NSCLC).
The End of Lung Cancer?
But that still doesn’t mean targeted therapy represents a cure — far from it. What it can do is slow the growth of cancers, giving some lung cancer patients the promise of living longer with cancer “The one-year survival rate for stage 3 or 4 lung cancer without targeted drugs is 10% or less,” says Dr. Martin. “With drugs, it’s 37%.”
But longevity isn’t everything. What’s also improved with these treatments is quality of life. “Patients might only be getting an extra year, but it’s an extra year not spent in hospital,” he says.
Perhaps most importantly from a patient perspective, side effects of typical chemo are greatly reduced with targeted therapies, because they are far less toxic to the body as a whole, says Dr. Stevens. That said, there are still side effects, which differ depending on what the therapy entails (see below).
Treatment and Side Effects
There are several targeted therapies, in oral form, that have been approved by the FDA for use in NSCLC, and more are being added to the list nearly every month. The most recent to be approved was Alecensa (alectinib). The drug is designed to treat people with advanced (metastatic) NSCLC who have the ALK mutation and whose disease has progressed, or who could not tolerate other treatments. ALK gene mutations are present in about 5% of patients with NSCLC, and the brain is a common place for this type of cancer cell to spread.
“Clinical trials of Alecensa show evidence of an effect on tumors that have spread to the brain,” explains Richard Pazdur, M.D., director of the Office of Hematology and Oncology Products in the FDA’s Center for Drug Evaluation and Research. In those trials, participants received Alecensa twice daily to measure the drug’s effect. In the first study, 38% of participants experienced a partial shrinkage of their NSCLC tumors, an effect that lasted for an average of 7.5 months. In the second study, 44% of participants experienced a partial shrinkage of their NSCLC tumors, lasting for an average of 11.2 months. The trials also examined Alecensa’s effect on brain metastases. 61% of participants in the two trials with brain metastases experienced a complete or partial reduction in their brain tumors, lasting an average of 9.1 months.
The most common side effects of Alecensa are fatigue, constipation, swelling and muscle pain (myalgia). Rarely, Alecensa may cause more serious side effects, including liver problems, severe or life-threatening inflammation of the lungs, very slow heartbeats and severe muscle problems. Patients on Alecensa may also be more prone to sunburn.
Common side effects include:
- Nausea and vomiting
- Changes in vision
Other side effects are also possible. Some side effects can be severe, such as low white blood cell counts, lung inflammation, liver damage, and heart rhythm problems.
The ALK mutation is most often seen in non-smokers (or light smokers) who have the adenocarcinoma subtype of NSCLC. Other drugs that target ALK include:
- Crizotinib (Xalkori)
- Ceritinib (Zykadia)
Another recent addition to the FDA-approval list for NSCLC is Tagrisso (osimertinib), meant for patients whose tumors have the EGFR mutation, and whose disease has progressed after treatment with other EGFR-blocking therapy.
Since EGFR is a protein involved in the growth and spread of cancer cells, the drug is thought to block the cancer’s growth by targeting those cells specifically. In trials, says Dr. Pazdur, “Tagrisso had a significant effect on reducing tumors.”
The most common side effects of Tagrisso are diarrhea, dry skin, rash and infection or redness around the fingernails. Tagrisso may rarely cause serious side effects, including inflammation of the lungs.
Other drugs that target cells with EGFR mutations
- Erlotinib (Tarceva)
- Afatinib (Gilotrif)
- Gefitinib (Iressa)
These drugs can be used alone (without chemo) as the first treatment for advanced NSCLCs that have certain mutations in the EGFR gene. These are more common in women and people who haven’t smoked.
However, it’s important to note that the side effects with these oral treatments are significantly less likely, and less severe, than with traditional chemotherapy. “There’s no single golden bullet yet but these targeted therapies offer a way to kill/slow down cancer cells with much less side effects,” said Dr. Martin.
- Targeted Therapies for Non-Small Cell Lung Cancer (American Cancer Society)
- Lung Cancer Causes, Symptoms,Types and Treatments (MedicineNet)
- How Personalized Medicine is Changing Lung Cancer (Genome Magazine)
- Gene Breakthroughs Spark a Revolution in Cancer Treatment (Wall Street Journal)