Are ESA's safe enough for cancer patients?

Earlier this year the FDA held a fourth session with the Oncologic Drugs Advisory Committee (ODAC) to review erythropoietin stimulating agents (ESA's). In 1993, ESA's were approved to reduce the number of red blood cells transfusions in cancer patients who have chemotherapy induced anemia. There is no doubt that the drugs do reduce the number of transfusions. They are also believed to alleviate symptoms such as fatigue and improve quality of life associated with the anemia, although the FDA has said that these remain 'unproven'.

The biggest challenge facing ODAC and the FDA though, is deciding whether ESA's very benefit in anemia is also a negative in terms of increased mortality and/or tumour progression. Eight controlled clinical trials suggest that there is evidence of increased risk of mortality and tumour progression in patients who have head & neck cancer, breast cancer, non-small cell lung cancer (NSCLC) and cervical cancer. According to the FDA, the new studies are either much larger than the original ones used to establish safety of the ESA's or have a different underlying histology.

In addition, the FDA claims that there is insufficient data to rule out mortality, shorter time to progression or lower loco-regional control in cancer other than NSCLC. As a result, FDA have asked ODAC to consider the following options:

- Remove the indication to treat anemia caused by cancer chemotherapy
- Restrict the indication to only patients who will not be cured by treatment intervention and contraindicate in adjuvant therapy
- Restrict use to specific cancer sub-types where safety has been adequately assessed (only NSCLC)
- Contraindicate use where harmful effected have been demonstrated (breast and head & neck cancers)
- Mandate risk management strategies

What is clear is that ESA's do offer a valuable clinical benefit in chemotherapy-induced anemia when used appropriately to avoid transfusions. The question is really one of risk-benefit because the very mechanism by which they work might also induce negative consequences.

It will be interesting to see what happens; The ESA market is worth several billion a year and sales are likely dropping with the repeated FDA discussions about risk benefit and safety.

Poniard report encouraging data in several cancers

The results of the Phase I trials with picoplatin, a new generation platinum, in prostate and colorectal cancer were presented earlier this year. Encouraging bioavailability data has also been presented from the ongoing Phase I trial of oral picoplatin.

The final phase II efficacy results in SCLC confirmed previously announced interim results showing a survival benefit in patients with recurrent SCLC who failed prior platinum-containing first-line chemotherapy or who progressed within six months of first-line therapy. The median overall survival in the picoplatin Phase II trial was 27 weeks for refractory and resistant small cell lung cancer patients, a population for which there is no approved therapy in the US.

The pivotal Phase III SPEAR trial in small cell lung cancer continues to enroll patients and patient enrollment in the Phase II trial in metastatic colorectal cancer has now completed.

Poniard's Chief Medical Officer stated that:

"Picoplatin, to date, has demonstrated good tolerability, with no severe neuropathies when combined with 5-fluorouracil and leucovorin in the FOLPI regimen. In our Phase 2 trial, we are performing a head-to-head comparison of the efficacy and safety of picoplatin with oxaliplatin. We will be presenting preliminary Phase 2 data and updated Phase 1 data at the 2008 American Society of Clinical Oncology (ASCO) Annual Meeting."