Discussion
The benefits of EGFR therapy have been established for treatment of late-stage NSCLC, but such therapy has limitations. For advanced-stage NSCLC, erlotinib has been shown to improve disease-free progression by 2.7 to 3.25 months and overall survival by 6.7 to 7.9 months.4-6 However, 1-year survival estimates remain as low as 35.0 to 37.7%,5,6 and its utility as first-line therapy has been questioned; randomized control trials have shown EGFR therapy to be of benefit only as secondor third-line therapy, when used with platinum-based chemotherapeutics.3,4 The few reports of complete response, however, have not included a definition of duration of survival.5,6
Occasionally, there have been reports of patients surviving for significantly longer periods, including 1 report of a patient who survived with complete remission for 2 years.7 In another case report, a patient experienced partial remission for more than 1 year with erlotinib as a third-line therapy.8 Although several reports indicated prolonged survival with erlotinib, or induction of complete remission of metastasis, survival has not been longer than 2 years.9-12
Important considerations for use of erlotinib are factors that predict a positive treatment response, including female sex, no previous exposure to tobacco, Asian origin, and adenocarcinoma on histologic examination.3,13 Mr. J did not meet any of these criteria. Interestingly, one study examining characteristics predictive of a positive response to erlotinib did not show that EGFR gene mutations were associated with response, although other studies have shown this to be a significant predictor of response.3,14,15
In this patient, his impressive response to erlotinib was most likely augmented by the presence of the EGFR mutation. Additionally, some reports indicate that pretreatment with platinum-based therapy can induce genetic changes resulting in EGFR mutations, thus enabling the benefit of erlotinib.10 Given that his biopsy results were not tested for the EGFR mutation prior to initiating carboplatin, this is a possibility.
Other factors specific to Mr. J that may have influenced his response to therapy include his personal wealth, which may have given him direct access to physicians outside the VA. His family support also may have motivated him to pursue and continue treatment, thus augmenting his survival. This support likely contributed in large part to his continuing erlotinib therapy despite the severe rash, hair loss, and trichomegaly. Other AEs associated with long-term erlotinib therapy include folliculitis, diarrhea, fatigue, and paronychia,although Mr. J did not experience these.16
Conclusion
Mr. J continues to follow up regularly at WLAMC. To the authors’ knowledge, this patient’s 8 year survival is the longest length of survival for any patient with NSCLC on erlotinib therapy. While the therapeutic benefits of erlotinib as a second-line therapy have been shown, EGFR therapy may be more effective than previously thought. Further research is needed to fully understand the benefits of erlotinib.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.