In line with its multiple indication strategy for Avastin (bevacizumab), Roche released a flurry of data from clinical trials with its flagship anticancer at the joint ECCO (European Cancer Organisation) and ESMO (European Society for Medical Oncology) conference in Berlin, Germany.

There was some initial media excitement when it appeared the results would include a statistically significant improvement in overall survival with Avastin in melanoma. However, an eleventh-hour update of the abstract presented at the ECCO-ESMO conference downgraded the data to “encouraging” and worthy of further investigation.

The primary endpoint in the Phase II BEAM study of Avastin plus carboplatin/paclitaxel versus chemotherapy alone in previously untreated patients with advanced malignant melanoma was progression-free survival (PFS). In patients given Avastin, PFS was a median 5.6 months compared with 4.2 months on chemotherapy alone, showing a 22% risk reduction for progression, Roche reported.

In the secondary endpoint of overall survival (OS), median survival in the Avastin and control arms were 12.3 months and 9.2 months respectively, representing a 21% risk reduction for mortality. Neither of these outcomes reached statistical significance, however.

“The results from the BEAM study are very encouraging and warrant continued investigation,” commented investigator Dr Steven O’Day, chief of research and director of the melanoma programme at The Angeles Clinic and Research Institute in California, US.

“Malignant melanoma currently has so few treatment options, with less than 5% of patients living beyond five years, so I am very pleased that we are seeing evidence that an improvement in outcomes may soon be possible for this devastating disease.”

Inoperable tumour response

Roche also presented data at the ECCO-ESMO conference showing that in the single-arm Phase II BOXER trial, Avastin given in combination with XELOX chemotherapy led to the shrinkage or disappearance (overall response rate) of liver metastases in 78% of 45 patients with advanced colorectal cancer.

These patients were considered unsuitable or borderline for upfront resection of liver-only metastases. Following treatment with the Avastin-XELOX combination, 33% of the patients were eligible for surgery. Complete surgical removal of the metastases was achieved in 56% of the treated patients, including both borderline resectable patients and those whose metastases were originally inoperable.

The results mean that some patients previously regarded as incurable because their colorectal cancer had spread to their liver, and inoperable due to the nature of their tumours, “now have the possibility of being cured completely of their cancer”, Roche said.

A previous study has shown that resection surgery can potentially double the chances of two-year survival in bowel cancer that has spread to the liver compared with inoperable patients, it pointed out.

Neurocognitive benefit

Another data highlight was the potential neurocognitive benefits seen in a new analysis of the Phase II BRAIN study of Avastin in glioblastoma (GBM), the most aggressive of brain cancers.

Last May, the US Food and Drug Administration granted Avastin accelerated approval for the treatment of GBM patients with progressive disease following prior therapy, based on data from the BRAIN trial and a further study by the National Cancer Institute.

The BRAIN trial, which evaluated Avastin either alone or in combination with irinotecan chemotherapy, had already shown that, six months after starting treatment, 42.6% of patients taking Avastin as a single agent were alive without their disease advancing (i.e., progression-free survival). When Avastin was combined with irinotecan, this proportion rose to 50.3%.

In the latest analysis, 75.0% and 60.7% respectively of patients on Avastin or Avastin plus chemotherapy who showed an objective response to treatment experienced stable or improved neurocognitive function at the time of response relative to baseline, Roche reported.

A decline in neurocognitive function, which includes the ability to think and reason, make judgments and remember things, is a common consequence of GBM.

Among patients on Avastin or Avastin plus chemotherapy who achieved PFS of more than six months, 70.4% and 70.0% respectively showed stable or improved neurocognitive function at week 24 relative to baseline.

In addition, the analysis found that Avastin-based therapy for glioblastoma was associated with reduced use of steroids in some patients. As Roche pointed out, steroids are an important part of symptom management in GBM but can lead to complications such as weight gain, insomnia and behavioural changes.