As described in a prior post, chemotherapy after surgery is often recommended after surgery, at least for a subset of patients with stage IB to IIIA (without mediastinal lymph node involvement) NSCLC, based on a potential to increase cure long-term survival compared to surgery alone. At this point, two forms of targeted therapy (erlotinib, or Tarceva, as a single agent in second- and third-line advanced NSCLC, and bevacizumab, or Avastin, combined with carboplatin and paclitaxel for first-line treatment of advanced NSCLC) have been approved by the FDA for advanced NSCLC because they have demonstrated an improvement in survival. At this point, however, we don’t know whether adding targeted therapies as a strategy in earlier stage NSCLC can increase cure rates. But one key trial that is evaluating this possibility is the RADIANT trial.

RADIANT Trial; click to enlarge.

RADIANT is an acronym for Randomized, Double-Blind Trial in Adjuvant NSCLC with Tarceva. This will be an international trial designed to enroll 945 patients who have undergone surgery, with no residual cancer left behind, for stage IB, II, or stage IIIA NSCLC. Patients may have received up to four cycles of chemotherapy after surgery, but patients who received no chemo are still eligible. Patients are then randomized to receive either tarceva or a placebo, with two-thirds of patients receiving the active drug and one-third receiving placebo. Because it is a double-blinded study, neither patients nor their treating doctor know who is getting tarceva or a placebo. This is appropriate because we don’t know whether Tarceva is going to be better, the same, or actually worse, with side effects of treatment but no added benefit.

Importantly, although Tarceva is approved by the FDA for all patients with previously treated advanced NSCLC, regardless of whether their tumor has high levels of EGFR, the target of Tarceva, or amplification of the EGFR gene in tumor cells. We still debate whether Tarceva works best, or perhaps only works at all, in patients with EGFR protein expression as detected by a test called immunohistochemistry (or IHC) or amplification (excess copies) of the EGFR gene by a test called fluorescence in situ hybridization (or FISH). Many trials that are investigating the future role for Tarceva are using more selected populations based on clinical characteristics such as never-smoking or BAC, or molecular characteristics such as EGFR overexpression by IHC, gene amplification by FISH, or presence of an EGFR mutation detected by gene sequencing. Perhaps the benefits of Tarceva can be found to be more pronounced and more consistent if we can identify and treat those patients most likely to do well with it, rather than use a “targeted therapy” unselectively.

Further information about eligibility details and participating centers can be found here.