A series of three new clinical trials (research studies with volunteer patients) is big news for some people affected by early-stage lung cancer. The trials focus on two drugs typically used to treat late-stage adenocarcinoma. These two drugs, Tarceva and Xalkori, may also help stage I, II, and IIIA patients prevent relapse (return of cancer) after their tumors have been surgically removed. The new clinical trials will put the treatments to the test.
Tarceva and Xalkori are both targeted-therapy drugs. Targeted therapies, once only experimental, are now standard treatments for the most common form of non-small cell lung cancer (NSCLC): adenocarcinoma. When a patient is diagnosed with adenocarcinoma that is unresectable stage IIIb (can’t be removed by surgery) or metastatic stage IV, molecular tests are done to determine if the tumor has mutations in the gene EGFR or alterations (rearrangements) in another gene called ALK. If these are detected, the patient is very likely to receive not chemotherapy, but the EGFR-targeted drug Tarceva or the ALK-targeted drug Xalkori. The U.S. Food and Drug Administration (FDA) has approved both drugs for treating advanced and metastatic cancer that cannot be removed by surgery or has spread to other organs. Data from large clinical trials show that these drugs perform better than standard-of-care chemotherapy.
However, it is not known if these drugs are helpful to patients who have earlier stages of adenocarcinoma. People with stage I, II, or IIIA adenocarcinoma usually go through surgical resection of their tumors, followed by chemotherapy and/or radiotherapy. But these patients quite frequently relapse, that is, develop new metastatic tumors. It is possible that, for those with alterations in EGFR or ALK, targeted treatment after surgery and possibly chemotherapy may improve chances of staying disease-free for a long time.
To test this possibility, researchers have organized three new clinical trials collectively known as ALCHEMIST (Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing Trials). ALCHEMIST will address the potential of Tarceva or Xalkori in reducing the rate of relapses in early-stage adenocarcinoma.
In the first of the three trials, (NCT02194738), researchers will identify patients who are eligible to participate by collecting tumor biopsies and blood samples for analysis. They will look for patients whose surgically removed tumors have EGFR or ALK mutations and who may have completed chemo- and radiotherapy treatments (if relevant). Patients with EGFR mutations will then be enrolled in NCT02193282, where they will be given Tarceva or, for comparison, a placebo. (The trial is randomized, so patients will not get to choose whether they receive Tarceva or not.) Similarly, patients whose tumors have ALK rearrangements will receive Xalkori or a placebo in clinical trial NCT02201992. The patients will be followed up for 5 years to determine if the drugs improved their overall survival.
ALCHEMIST is expected to screen about 6,000 to 8,000 potential participants at hundreds of sites in the U. S. over 5 to 6 years, and to enroll about 800 patients into the two treatment trials. Every patient who participates in the screening stage (irrespective of enrollment into treatment) will also be studied for other cancer risk characteristics, and their tumor tissue will be analyzed in a research genomics initiative conducted by the National Cancer Institute’s Center for Cancer Genomics (CCG).
Patients with squamous lung cancer have been given the choice to participate in a trial of similar design that aims to provide them with targeted therapies tailored to the molecular blueprints of their tumors. Earlier this year, we wrote about the MASTER protocol, which started recruiting patients in Jun