ES02.03 Management of Other Non EGFR Oncogene Addicted Tumors

Abstract

Stage III non-small cell lung cancer accounts for heterogeneous group of diseases, due to differences in tumor size, location number of nodes involved, and lymph node station involved. Stage III non-small cell lung cancer comprises 2 distinct stages, stage IIIA and IIIB disease that have different prognosis, and are usually treated differently. Approximately 15% of all patients with newly diagnosed non-small cell lung cancer present with stage III disease. Options for stage III non-small cell lung cancer include surgery, with lobectomy or pneumonectomy depending on the tumor stage, and lymph node involvement. Chemotherapy may be administered in the neoadjuvant, concurrent or adjuvant setting. Radiation therapy can be given in a concurrent, sequential approach, or may be administered in the postoperative fashion. Combination approaches are often used, and due to the significant need of multi-modality therapy, treatment decisions are usually made in a multidisciplinary setting. The optimal therapeutic approach for patients with stage IIIA non-small cell lung cancer remains controversial. For subset of patients with T3 to T4 N0-1 disease, and superior sulcus location, surgery remains a viable and preferred option. However, the optimal treatment for patients with stage III A, with bulky lymph node involvement, or multi station lymph node involvement including N2 disease, remains an area of ongoing controversy. Tri-modality approaches using preoperative chemotherapy, or upfront chemoradiation therapy followed by surgery have been evaluated (1). For patients with surgically unresectable, or medically inoperable disease, concurrent chemoradiation therapy has been established as the standard of care for patients spanning the spectrum of stage IIIA and IIIB disease. Recently, the PACIFIC trial demonstrated an improvement in progression free survival and overall survival with the administration of durvalumab as consolidation therapy (regardless of PDL-1 status) for patients who had not progressed after 2 or more cycles of definitive concurrent platinum-based chemoradiation therapy (2, 3). This approach represents a new paradigm in the management of unresectable NSCLC, and has now been adopted as standard of care. Management of Stage III patients with non EGFR oncogene addicted tumors is an area of active research. ALK or ROS directed oral tyrosine kinase inhibitors (TKIs) are not typically administered in the adjuvant setting outside of a clinical trial. There are several trials evaluating the use of targeted therapies. ALINA, is one such trial, that is a phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive ALK positive NSCLC (4). Another study is comparing adjuvant alectinib versus adjuvant platinum-based chemotherapy in patients with ALK positive NSCLC, here the alectinib is administered for 2 years (NCT 03456076). The Adjuvant Lung Cancer Enrichment Marker Identification and Sequencing (ALCHEMIST) trial is actively enrolling patients with operable NSCLC and will perform genetic screening of their tumors. Patients with EGFR mutation or ALK gene rearrangement in their tumor will be randomized to placebo versus erlotinib or crizotinib, respectively (NCT02194738). We await the results of these trials prior to routine incorporation of molecularly directed therapy in the management of locally advanced disease. 1. Albain KS, Swann RS, Rusch VW, Turrisi AT, 3rd, Shepherd FA, Smith C, et al. Radiotherapy plus chemotherapy with or without surgical resection for stage III non-small-cell lung cancer: a phase III randomised controlled trial. Lancet. 2009;374(9687):379-86. Epub 2009/07/28. https://doi.org/10.1016/S0140-6736(0960737-6). PubMed PMID: 19632716; PubMed Central PMCID: PMC4407808. 2. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. The New England journal of medicine. 2017;377(20):1919-29. 3. Antonia SJ, Villegas A, Daniel D, Vicente D, Murakami S, Hui R, et al. Overall Survival with Durvalumab after Chemoradiotherapy in Stage III NSCLC. 2018; 379:2342-2350 4. Solomon BJ, Ahn JS, Barlesi F et al. ALINA: A phase III study of alectinib versus chemotherapy as adjuvant therapy in patients with stage IB–IIIA anaplastic lymphoma kinase-positive (ALK+) non-small cell lung cancer (NSCLC). J Clin Oncol 37, 2019 (suppl; abstr TPS8569)