Photo by Bill Branson
Vials of drugs
A study of cancer drugs approved by the European Commission from 2009 to 2013 showed that few hematology drugs were known to provide a benefit in overall survival (OS) or quality of life (QOL) over existing treatments.
Of 12 drugs approved for 17 hematology indications, 3 drugs had been shown to provide a benefit in OS (for 3 indications) at the time of approval.
None of the other hematology drugs were known to provide an OS benefit even after a median follow-up of 5.4 years.
Two hematology drugs were shown to provide a benefit in QOL (for 2 indications) after approval, but none of the drugs were known to provide a QOL benefit at the time of approval.
These findings were published in The BMJ alongside a related editorial, feature article, and patient commentary.
All cancer drugs
Researchers analyzed reports on all cancer drug approvals by the European Commission from 2009 to 2013.
There were 48 drugs approved for 68 cancer indications during this period. Fifty-one of the indications were for solid tumor malignancies, and 17 were for hematologic malignancies.
For 24 indications (35%), research had demonstrated a significant improvement in OS at the time of the drugs’ approval. For 3 indications, an improvement in OS was demonstrated after approval.
There was a known improvement in QOL for 7 of the indications (10%) at the time of approval and for 5 indications after approval.
The median follow-up was 5.4 years (range, 3.3 years to 8.1 years).
Overall, there was a significant improvement in OS or QOL during the study period for 51% of the indications (35/68). For the other half (49%, n=33), it wasn’t clear if the drugs provide any benefits in OS or QOL.
All cancer trials
The 68 approvals of cancer drugs were supported by 72 clinical trials.
Sixty approvals (88%) were supported by at least 1 randomized, controlled trial. Eight approvals (12%) were based on a single-arm study. This included 6 of 10 conditional marketing authorizations and 2 of 58 regular marketing authorizations.
Eighteen of the approvals (26%) were supported by a pivotal study powered to evaluate OS as the primary endpoint. And 37 of the approvals (54%) had a supporting pivotal trial evaluating QOL, but results were not reported for 2 of these trials.
Hematology trials and drugs
Of the 12 drugs approved for 17 hematology indications, 4 were regular approvals, 5 were conditional approvals, and 8 had orphan drug designation.
The approvals were supported by data from 18 trials—13 randomized and 5 single-arm trials.
The study drug was compared to an active comparator in 9 of the trials. The drug was evaluated as an add-on treatment in 4 trials. And the drug was not compared to anything in 5 trials (the single-arm trials).
OS was the primary endpoint in 1 of the trials, and 17 trials had OS or QOL as a secondary endpoint.
There were 3 drugs that had demonstrated an OS benefit at the time of approval but no QOL benefit at any time:
- Decitabine used for first-line treatment of acute myeloid leukemia in adults 65 and older who are ineligible for chemotherapy
- Pomalidomide in combination with dexamethasone as third-line therapy for relapsed/refractory multiple myeloma (MM)
- Rituximab plus chemotherapy for first-line treatment of chronic lymphocytic leukemia (CLL).
There were 2 drugs that had demonstrated a QOL benefit, only after approval, but they were not known to provide an OS benefit at any time:
- Nilotinib as a treatment for adults with newly diagnosed, chronic phase, Ph+ chronic myeloid leukemia (CML)
- Ofatumumab for CLL that is refractory to fludarabine and alemtuzumab
For the remaining drugs, there was no evidence of an OS or QOL benefit at any time during the period studied. The drugs included:
- Bortezomib given alone or in combination with doxorubicin or dexamethasone as second-line therapy for MM patients ineligible for hematopoietic stem cell transplant (HSCT)
- Bortezomib plus dexamethasone with or without thalidomide as first-line therapy in MM patients eligible for HSCT
- Bosutinib as second- or third-line treatment of Ph+ CML (any phase)
- Brentuximab vedotin for relapsed or refractory systemic anaplastic large-cell lymphoma
- Brentuximab vedotin for relapsed or refractory, CD30+ Hodgkin lymphoma after autologous HSCT or as third-line treatment for patients ineligible for autologous HSCT
- Dasatinib for first-line treatment of chronic phase, Ph+ CML
- Pixantrone for multiply relapsed or refractory B-cell non-Hodgkin lymphoma
- Ponatinib for patients with Ph+ acute lymphoblastic leukemia who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib or characterized by T315I mutation
- Ponatinib for patients with any phase of CML who are ineligible for imatinib or have disease that is resistant or intolerant to dasatinib/nilotinib or characterized by T315I mutation
- Rituximab as maintenance after induction for patients with follicular lymphoma
- Rituximab plus chemotherapy for relapsed or refractory CLL
- Temsirolimus for relapsed or refractory mantle cell lymphoma.
