adjuvant chemotherapy in patients with intermediate or high risk stage i or stage iia non-squamous non-small cell lung cancer: aim-high (adjuvant intervention in molecular high risk patients)

Conditions: Non-Small Cell Lung Cancer

Summary: the optimal treatment for stage i or stage iia non-small cell lung cancer (nsclc) remains controversial. radiographic surveillance alone has been recommended for stage i and stage iia patients after the tumor is removed surgically from the lung, and this standard has been based on the fact that no previous clinical trial has demonstrated a benefit for stage i or stage iia nsclc patients who receive post-operative chemotherapy. these patients, however, have a substantial risk of death within five years after operation, ranging from approximately 30% to 45%, largely due to metastatic disease that is present immediately after surgery but that is undetectable by conventional methods. some leading organizations therefore currently recommend post-operative chemotherapy as an alternative standard of care in stage i or stage iia nsclc patients who are considered to be at particularly high-risk. up until now, however, there has not been a well-validated means to identify stage i and stage iia nsclc patients at high risk of death within five years after operation. a new prognostic tool, a 14-gene prognostic assay, which has been validated and definitively demonstrated in large scale studies to identify intermediate and high-risk stage i or stage iia patients with non-squamous nsclc, is now available to all clinicians through a clia-certified laboratory. it is therefore now possible to compare the outcomes of patients randomly assigned to one or the other of these competing standards of care.


Eligibility criteria:
inclusion criteria: * written informed consent * age ≥ 18 years * able to comply with the protocol, including acceptable candidacy for adjuvant chemotherapy according to local institutional standards and likely compliance with follow-up for anticipated length of study (i.e. 5 years from the initiation of enrollment). * willing to be randomized to chemotherapy. * histologically documented completely resected (r0) stage i or iia non-squamous nsclc (per 8th edition, tnm staging system) * adequate tissue sample for the 14-gene prognostic assay * life expectancy excluding nsclc diagnosis ≥ 5 years * ecog performance status 0-1 exclusion criteria: * final pathologic diagnosis of pure squamous cell, pure small cell, or pure neuroendocrine histology, or any combination of only these three histologies * evidence of greater than stage iia pathologic staging * evidence of incomplete resection * pregnant or lactating women * unwilling to use an effective means of contraception * active infection, either systemic or at site of primary resection * systemic chemotherapy or anti-cancer agent within 5 years prior to enrollment * radiotherapy to the chest in the immediate pre- or post- operative period * malignancies other than the current nsclc within 5 years prior to randomization, except for adequately treated cis of the cervix, non-melanoma skin cancer, localized prostate cancer treated locally, ductal carcinoma in situ treated surgically * treatment with any investigational drug or participation in another clinical trial within 28 days prior to enrollment * known hypersensitivity to study treatment agents * evidence of any other disease including infection that contraindicates the use of systemic cytotoxic chemotherapy or puts the patient at high risk for treatment-related complications * wound dehiscence or infection

Keywords: non-squamous adjuvant chemotherapy ifct