Generic Imatinib Compared With Gleevec in CP-CML: Patient Outcomes Across 3 Countries
Although the study suggested the efficacy of the branded version was superior to its generic counterpart, more research may be necessary to tease out manufacturer differences.
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SAN DIEGO — Patients with chronic phase chronic myeloid leukemia (CP-CML) who were treated in the first-line setting with generic imatinib were found to have a higher rate of treatment failure at 3 months and worse progression-free survival (PFS), event-free survival (EFS), and overall survival at 24 months compared with patients who were administered the branded version of the drug (Gleevec®, or Glivec® outside of the United States), according to data presented at the 2018 American Society of Hematology Annual Meeting and Exposition in San Diego, California.1
To evaluate outcomes of patients treated with frontline Gleevec or generic imatinib, investigators analyzed data from a total of 445 patients across 19 centers in 3 countries (Gleevec, 285 patients; generic imatinib, 160 patients). They compared prospective efficacy results from patients who initiated treatment with generic imatinib in Brazil and Argentina between January 2015 and September 2017, as well as in Italy from February 2017 to July 2017; with the retrospective efficacy results from patients who were administered the branded version of the drug in Brazil from January 2010 to December 2011, and in Italy between February 2010 and July 2017.
In all cohorts, treatment with either the branded or generic form of imatinib was initiated at 6 months from diagnosis. Responses to drug were measured using European Leukemia Net (ELN) 2013 criteria.
Although results from the multicenter, observational, cohort-type study suggested that the efficacy of the branded version of the medication was superior to its generic counterpart — the rate of treatment failure at 3 months was 7% and 16% with Gleevec and generic imatinib, respectively (P = .004) — this apparent treatment benefit of Gleevec was not maintained: at 6 months, there were no significant differences in treatment failure between the medications (12% for Gleevec vs 15% for generic imatinib; P = .395).
At 24 months, however, overall survival (OS), PFS, and EFS were determined to be higher for the branded drug compared with the generic drug: (99% vs 94%, P = .013), (98% vs 94%, P = .023) and (72% vs 56%; P < .0001), respectively. There were no differences in OS and PFS in the low-risk Sokal groups.
The median follow-up was 25 months (range, 0-71) and 11 months (range, 0-31) for patients in the Gleevec and generic imatinib groups, respectively (P < .0001).
There were 3 cases each of progression in the Gleevec and generic drug treatment groups. The frequency of grade 3 to grade 4 adverse events across groups was similar.
Interestingly, 40% of patients who discontinued treatment with their initial frontline therapy actually did so to make the switch from Gleevec to generic imatinib. As a result, 114 patients who switched from Gleevec to generic were censored from the study.
Other reasons for treatment discontinuation in the Gleevec and generic imatinib arms, respectively, included resistance (19.7% vs 47.5%), intolerance (15.3% vs 23.7%), nonadherence (4.4% vs 3.4%), death (2.0% vs 6.8%), entered a clinical trial (0.5% vs 10.2%), progression (2.0% vs 5.0%), pregnancy (0 vs 3.4%).
And, in the presentation, Katia Pagnano, MD, NCT do Sangue Hemocentro UNICAMP, University of Campinas, Campinas, SP, Brazil, pointed out there were important differences in the patients across the 2 cohorts: the patients receiving generic medications were younger, had a higher Sokal risk, and a longer time to start treatment with imatinib. In addition, the 2010 to 2011 cohorts were managed according to European Leukemia Net (ELN) 2009 criteria, while 2015 cohorts were evaluated based on ELN 2015 criteria.
Regulatory and logistical components were also a factor: Dr Pagnano said that there were only 7 patients from Italy taking generic imatinib, because Italy only has 1 generic version of the drug and it just became available there in 2017. As a result, most of the patients in the generic imatinib cohort were from Brazil. By contrast, in Brazil, there are 3 versions of generic imatinib available from different manufacturers.
An attendee commented that there are many versions of imatinib available, and asked how many different kinds were used in the study. Dr Pagnano confirmed there were 2 different generics for imatinib used in the trial. When another attendee implored Dr Pagnano to share the names of the manufacturers that provided the generics, she did not disclose which ones were used, and said her team is “still collecting data” on the generics patients started using after switching. “This will be analyzed in the future to see if there is any difference among the generics,” she added.
Some experts have argued that comparisons should not be made across trial types, as parameters for both of the trials were different. In addition, the study was observational as opposed to being a randomized controlled trial; some say that observational trials are not robust enough to prove the efficacy of one drug over another.
Lastly, the current study may not have been designed to resolve all potentially confounding prognostic factors that could influence the final outcome and subsequently, the study conclusion. Specifically, the proportion of patients with CP-CML who had b2a2 transcripts was higher in the cohort receiving generic imatinib compared with that of patients who were given branded imatinib (41.4% vs 53.8%, respectively, P = .017) — and as the study authors point out in their abstract, higher levels of b2a2 transcripts in CML have been linked to “an inferior rate of molecular responses and survival in other studies."
Disclosure: The presenters listed various disclosures from pharmaceutical companies. For a full list of disclosures, please refer to the study abstract.
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- Pagnano KB, Fava C, Miranda EC, et al. Efficacy and safety of generic imatinib compared to Glivec in chronic phase - chronic myeloid leukemia - a multicenter, observational study. Oral presentation at: American Society of Hematology 60th Annual Meeting & Exposition; December 1-4, 2018; San Diego, CA. Abstract 46.