Pfizer has retracted a 2009 Journal of Clinical Oncology study purporting to show a benefit of their experimental drug for lung cancer figitumumab after discovering that its clinical lead on the project had done analyses improperly.
Here?s the text of the notice:
Pfizer, Inc., has recently learned that the overall response rate and progression-free survival data published in ?Phase II Study of the Anti?Insulin-Like Growth Factor Type 1 Receptor Antibody CP-751,871 in Combination With Paclitaxel and Carboplatin in Previously Untreated, Locally Advanced, or Metastatic Non-Small-Cell Lung Cancer? (J Clin Oncol 27:2516-2522, 2009) are incorrect. These results, which have no impact on the safety profile of figitumumab, were discovered by Pfizer researchers during routine study close-out activities.
Specifically, in some cases, responses were not confirmed by performing a 4-week follow-up computed tomography scan per RECIST, or the follow-up scan did not verify continued tumor shrinkage. In addition, the response rate may have been overestimated as a result of including both confirmed and unconfirmed responses in the analysis. These errors in the objective response rates and progression-free survival data appear to be the result of inaccurate clinical data analyses that were performed outside of Pfizer?s standard operating procedures and are not the result of problems arising from study conduct. The revised data, included in the table below, were obtained through strict application of RECIST criteria and assignment of patients to a dosing level on the basis of original treatment received.
Because these results are fundamental to the conclusions of the paper, Pfizer and the lead author, Daniel D. Karp, MD, respectfully request that this article be retracted. We have shared the proposed retraction notice with all of the authors, and all agreed with this retraction notice. Pfizer has no reason to believe that the external authors contributed to the publication of these incorrect data and deeply regrets the impact of this action on the work of other investigators and to the readers of Journal of Clinical Oncology.
In a table included in the notice, there?s a clear difference in the results before and after the corrected analysis. In the original paper, for example, the control group, who received standard lung cancer treatments paclitaxel and carboplatin, had a median progression-free survival of about 3.5 months, while those who had the highest dose of CP-751,871 had a median of 5.0 months without progression. In the new analysis, there was no statistically significant difference between those two groups, with the control at 4.3 months and the high-dose group at 4.5 months.
Pfizer tells Retraction Watch that the study
?demonstrated that figitumumab was likely to be effective when used in combination with two chemotherapy drugs, paclitaxel and carboplatin, in patients with NSCLC; but not to the same degree as the previously published results indicated. ?The study did not demonstrate that the combination of the drugs was effective in the studied subset of patients with non-adenocarcinoma.
CP-751,871 is also known as figitumumab, which, as the company explains,
is a Pfizer-discovered monoclonal antibody that was developed for the treatment of various forms of cancer, including lung, prostate, breast and colorectal cancers and Ewing?s sarcoma.
The company stopped developing the drug in January 2011 after two Phase 3 studies in non-small-cell lung cancer (NSCLC) failed. The first of those trials ended in December 2009 after ?independent monitors had found more serious adverse events, including deaths, with patients receiving figitumumab,? Reuters reported at the time. (The company stopped enrolling new patients in October of that year.) Pfizer is ?no longer seeking regulatory approval for this compound.?
The 2009 JCO study has been cited 152 times, according to Google Scholar.
Pfizer gave Retraction Watch a bit more detail on what happened, including the fact that their clinical lead on the compound has left the company:
While conducting study close-out activities, Pfizer became aware that final data from a Phase 2 study of figitumumab, known as the 1002 study, and certain biomarker analyses performed in connection with the figitumumab program differed from the results that had been reported previously to regulators and published in medical journals.
We conducted a thorough and comprehensive review to determine how this may have occurred, and enlisted the services of independent experts to assist with this review. ?Our review determined that these errors were the result of inaccurately performed clinical data analyses. ?These incorrect analyses were performed outside of Pfizer?s standard operating procedures by the clinical lead, who left the Company in September 2010. ?The problems were not based on study conduct or the work of the external investigators.
We expect our employees to adhere to the highest levels of personal and professional integrity.? We also expect colleagues to take ownership and accountability, and to understand that failure to do so can lead to serious consequences including termination.
The clinical lead on the project appears to have been Antonio Gualberto, who is listed as a faculty member at Brown University?s medical school but does not appear to be employed there anymore, as his email bounces.
Pfizer continued:
Patient health and safety is our first concern. ?We want you to know that these new findings do not alter the safety profile of figitumumab.
Since Pfizer learned of these issues, we have been carefully analyzing our internal controls and ensuring that issues such as these did not exist in any other development programs. ?Our internal review has confirmed that this was an isolated incident and the controls in place at that time were rigorous.
We are committed to ensuring that accurate clinical study results are disclosed to medical professionals, patients and the public.? As per our standard practice, we are making the final study results available in a timely and responsible manner.
We?ve tried to reach lead author Daniel Karp, of MD Anderson, and will update with anything we learn.
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