77IN - Customized adjuvant chemotherapy: Prognostic and predictive factors

Date 30 September 2012
Event ESMO Congress 2012
Session Hot topics in early stage NSCLC
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Early Stage
Presenter Gerold Bepler
Authors G. Bepler1, J. Moon2, R. Zinner3, R. Calhoun4, K. Kernstine5, C. Williams6, P. Mack7, V. Oliveira4, D. Gandara8
  • 1Research, Barbara Ann Karmanos Cancer Institute, 48201 - Detroit/US
  • 2Research, SWOG Statistical Center, Seattle/US
  • 3Research, MD Anderson Cancer Center, Houston/US
  • 4Cardiovascular, University of California Davis, Sacramento/US
  • 5Thoracic Surgery, City of Hope, Duarte/US
  • 6Research, Moffitt Cancer Center, Tampa/US
  • 7Research, University of California Davis, Sacramento/US
  • 8Thoracic Oncolology Program, UC Davis Cancer Center, CA 95817 - Sacramento/US

Abstract

Background

Adjuvant chemotherapy provides a small, but significant, survival advantage for patients (pts) with completely resected stage II and III non-small-cell lung cancer (NSCLC). Prior data suggest that benefit from platinum-based adjuvant therapy is limited to pts with low levels of ERCC1 (E1) expression. RRM1 (R1) is the molecular target and key efficacy determinant for gemcitabine. We conducted a prospective clinical trial (SWOG-0720, NCT00792701) to determine if treatment selection based on in situ tumoral levels of E1 and R1 is feasible in a mixed environment of academic and community practices.

Methods

Eligibility was confined to pts with a complete resection of stage I disease and a tumor diameter of 2 cm or larger. Biomarker levels were determined at the protein level using automated quantitative analysis (AQUA, range of expression 1 - 255), and classified as high or low based on a priori cut-off values (E1 >65.0; R1 >40.0). Treatment consisted of four three-weekly cycles of cisplatin/gemcitabine (80 mg/m2 on day 1 and 1 g/m2 on days 1 & 8) for those with low E1 and/or R1 levels. Pts with high levels of both markers were observed. Feasibility was defined as treatment assignment within 12 weeks from surgery in at least 75% of eligible pts.

Results

85 pts accrued between March 2009 and April 2011. Two pts were ineligible because of inadequate mediastinal lymph node sampling. E1 and R1 levels were successfully determined in all 83 eligible pts, and 72 pts (87%) were successfully assigned within the allotted time period. 64 pts (77%) were assigned to chemotherapy and 19 (23%) to observation. E1 levels ranged from 4.3 – 211.2 (median 44.7), and R1 levels ranged from 2.5 – 234.4 (median 39.3). Pts demographics: median age 64 y, age range 41-84 y, ♂/♀ = 48/52%, adeno/squam/other = 59/28/13, stage IA/IB = 38/62%, PS 0/1 = 52/48%.

Conclusions

Adjuvant treatment assignment is feasible in pts with completely resected NSCLC in the cooperative group environment, and treatment assignment to chemotherapy vs observation was not significantly different from prior experience. Support: NCI grants U10-CA014028, U10-CA032102, U10-CA038926, U10-CA046368, U10-CA046441, U10-CA105409, P30-CA022453, R01-CA129343

Disclosure

All authors have declared no conflicts of interest.