Gefitinib (ZD1839) therapy for advanced bronchioloalveolar lung cancer (BAC): Southwest Oncology Group (SWOG) Study S0126

Reviewer: Maria Luisa Veronese, MD
Abramson Cancer Center of the University of Pennsylvania
Last Modified: June 7, 2004

This presentation discusses off-label use of gefitinib in BAC.

Presenter: H. West
Presenter's Affiliation: Swedish Cancer Institute, Seattle, WA
Type of Session: Scientific


Bronchioloalveolar lung cancer (BAC) is a distinctive subtype of non-small cell lung cancer (NSCLC) with different pathologic, radiographic characteristics, and natural history.  The rationale of this study is based on evidences of high expression of EGFR in BACs and anedoctal reports of clinical activity of gefitinib in patients with advanced stage BAC.  S0126 was initiated by SWOG to determine potential clinical, radiographic, pathologic, and molecular markers predictive of outcome under the influence of gefitinib therapy.

Materials and Methods

  • Patients with stage III-IV BAC. Institutional definition of BAC was used and central review was applied
  • Documentation of EGFR expression was not required to enter the study 
  • Gefitinib 500 mg po qd
  • Treatment was continued until evidence of progressive disease
  • Baseline and follow-up CT scans were centrally reviewed
Primary objective: overall survival (OS)
Secondary objectives: progression free survival (PFS), response rate (RR) according to RECIST, toxicity
Correlative studies: tumor tissue and buccal mucosa for analysis of EGFR pathway


  • 145 patients were accrued and 138 were eligible
  • 102 were chemonaive and 36 were previously treated patients.  Median age 67-68; most patients were females and have good PS
  • ORR for chemonaive and pre-treated patients was 19% and 9% respectively (CR 6% and 0%; PR 13% and 9%; SD 30% and 36%; PD 33% and 36%)
  • OS for chemonaive and pre-treated patients was 13 and 12 months respectively; PFS was 4 and 3 months respectively. 
  • Gefitinib was well tolerated with acneiform rash and diarrhea as main side effects. The toxicity was similar in the chemonaive and pretreated group.  11% of patients were removed from the study because of toxicity. There were 3 cases of progressive lung disease, possible interstitial lung disease secondary to treatment versus disease progression and/or infection.
  • Subset analyses revealed longer survival in females (19 vs 8 months); in patients who developed rash (13 vs 5 months); in patients with PS 0-1 (15 vs 5 months); and in never-smokers (median survival not reached vs 10 months). 
  • RR was also higher in patients who developed rash (21% vs 0%; p<0.001) and in females (20% vs 13%).  RR was not significantly different in never-smokers vs former/current smokers (13% vs 18%)

Author's Conclusions

  • This is the largest prospective clinical trial in patients with BAC
  • Gefitinib has modest activity as single agent in both chemonaive and previously treated advanced BAC
  • There is no difference in OS between chemonaive and pre-treated patients
  • Gender, smoking status, development of rash, and PS are associated with OS
  • Further studies with EGFR inhibitors are needed

Clinical/Scientific Implications
This study represents the largest prospective clinical trial in patients with BAC and the largest study of single agent gefitinib as front line therapy.  The response rate is comparable to the one reported in previous studies with gefitinib monotherapy and responses were observed in both chemonaive and pretreated groups.  No survival difference was observed between the chemonaive and pretreated groups.  Interestingly, not developing a rash emerged as the most important predictor of a poor outcome, while female gender and never-smoker were the best determinants of improved outcomes.  Gefitinib can be used as first line treatment when toxicity from chemotherapy is of concern, while first-line chemotherapy is still the standard approach for patients with BAC.  It may be important to change treatment if there is no development of rash after starting gefitinib.

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