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FDA ALERT [6/2005]:

FDA has approved new labeling for gefitinib (Iressa) that limits the indication to cancer patients who, in the opinion of their treating physician, are currently benefiting, or have previously benefited, from Iressa treatment. AstraZeneca plans to limit distribution of this drug under a risk management plan called the Iressa Access Program.

This information reflects FDA?s preliminary analysis of data concerning this drug. FDA is considering, but has not reached a final conclusion about, this information. FDA intends to update this sheet when additional information or analyses become available.

Monday May 19, 2003 7:15 PM GMT

 

Gefitinib is the first oral drug approved in the United States for the treatment of non-small cell lung cancer.

 

 
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The FDA approved gefitinib (trade name Iressa?, manufactured by AstraZeneca) for the treatment of advanced-stage non-small cell lung cancer after prior treatment with both platinum-based and Docetaxel (trade name Taxotere?, manufactured by Aventis) chemotherapy.  This approval was made public on May 5th, 2003.  The recommended treatment with Iressa (gefitinib) is a 250 mg as one pill each day until lung cancer progression or unacceptable toxicity from the drug.  Iressa (gefitinib) is manufactured as a 250 mg pill.

Iressa (gefitinib) is the first oral drug approved in the United States for the treatment of non-small cell lung cancer.  It is a novel small molecule that inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR).  EGFR activity via tyrosine kinase is involved in cancer cell activity and growth.

There have been two Phase 2 clinical trials that have studied the use of Iressa (gefitinib) in advanced-stage non-small cell lung cancer:  IDEAL-1 and IDEAl-2 (international and U.S. studies, respectively).  IDEAL-1 enrolled patients who had received at least one prior chemotherapy regimen (platinum-based) and had disease progression.  IDEAL-2 enrolled the same population, except that patients had received at least two prior chemotherapy regimens (platinum-based and Docetaxel). Both clinical trials were presented at the American Society of Clinical Oncology Annual Meeting held last year (abstract #1188 for IDEAL-1 and abstract #1166 for Ideal-2).

In both clinical trials, patients received Iressa (gefitinib) at a dose of either 250 mg each day or 500 mg each day.  Treatment was continued until disease progression, unacceptable toxicity or patient death.  Table 1 below outlines information about these two clinical studies.

Table 1

 

IDEAL-1

 

IDEAL-2

250 mg

500 mg

250 mg

500 mg

 

 

# of patients

104

100

102

114

Median age

61 years

60 years

61 years

62 years

Male patients

75%

66%

59%

55%

Performance status 0-1 / 2

87% / 13%

87% / 13%

81% / 19%

79% / 21%

Adenocarcinoma

64%

67%

69%

64%

Partial response

18%

19%

12%

9%

Stable disease

36%

32%

31%

27%

Overall disease control rate

54%

51%

43%

36%

Median duration of response

98 days

140 days

 

 

Progression free survival

2.7 months

2.8 months

1.9 months

 

Overall survival                      

7.6 months

8.1 months

6.5 months

5.9 months

Symptom improvement

40%

37%

43%

35%

Median time to achieve symptom improvement

8 days

14 days

Rash (grade 3/4)

1%

7%

0%

5%

Diarrhea (grade 3/4)

0%

7%

1%

6%

             

Data presented about subgroup analyses indicated that adenocarcinoma pathology favored a better response to Iressa (gefitinib) compared to squamous cell pathology.  Bronchioalveolar pathology also appeared to respond well.  These subgroup analyses are of small numbers and statistical comparisons could not be performed.

No differences in treatment outcomes were noted among patients who have received one or more prior chemotherapy regimens.  Likewise, no differences in treatment outcomes were noted for patients with good or poor performance statuses.  No differences in outcomes were noted between the two different Iressa (gefitinib) doses.

The achievement of a symptom improvement was correlated with the achievement of disease response.  In the IDEAL-1 trial, 69% of patients receiving Iressa (gefitinib) 250 mg had symptom improvement if they had a partial tumor response, whereas only 40% and 12% did if they had stable disease or progressive disease, respectively.  In the IDEAL-2 trial, 100% of patients receiving Iressa (gefitinib) 250 mg had symptom improvement if they had a partial tumor response, whereas only 81% and 12% did if they had stable disease or progressive disease, respectively.  In the IDEAL-1 trial, if symptom improvement occurred, then the median survival was better than if no symptom improvement occurred (not reached versus 3.5 months, respectively.  In the IDEAL-2 trial, if symptom improvement occurred, then the median survival was also noted to be better than if no such improvement occurred (not reached versus 3.7 months, respectively).

The majority of toxicities were of a mild nature (i.e.- grade 1 or 2).  Common toxicities included skin reactions (rash, acne, pruritis), changes in the liver laboratory tests, diarrhea (which can cause dehydration), nausea, and vomiting.  No treatment-related deaths were reported initially in the IDEAL-1 trial and only one treatment-related death was reported in the IDEAL-2 trial.  Recent reports from Japan have indicated approximately 200 cases of deaths among patients receiving Iressa (gefitinib).  Interstitial lung disease was the problem encountered in these cases and appeared to occur at an incidence of 1-2%.  Approximately 1/3 of such cases were fatal.  Interstitial lung disease presented as respiratory difficulties, cough, and fever without overt clinical evidence of infection.  In such cases, prompt discontinuation of Iressa (gefitinib) and the application of supportive measures are recommended.

Two large randomized clinical trials were reported at last year?s ESMO meeting in Europe: INTACT-1 and INTACT-2.  These trials randomized patients to a standard platinum-based chemotherapy regimen or to the same chemotherapy regimen with the addition of Iressa (gefitinib).  The study results, in both trials, did not show any benefit from the addition of Iressa (gefitinib) to first-line chemotherapy in the treatment of advanced-stage non-small cell lung cancer.

More detailed information about Iressa (gefitinib), including the results of the above mentioned clinical trials and prescribing information, is available at the FDA?s web site:

 pdf_icon.jpg (13x13 -- 0 bytes) http://www.fda.gov/cder/drug/infopage/iressa/default.htm

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