IHS Global Insight Perspective | |
Significance | Roche and Genentech have unveiled the results of four independent clinical trials at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), held at the weekend in Orlando, Florida (U.S.), including the most-awaited full results of the C-08 study, which evaluated the benefits of Avastin (bevacizumab) in early colorectal cancer. |
Implications | Three of the four trials unveiled at the weekend have failed to impress. On the Avastin front, the results suggest that extending the course of treatment could be of benefit to patients although the observation raises questions over the cost and long-term safety of treatment. |
Outlook | The full results of the C-08 study shed uncertainty on the two companies' ability to secure an indication extension for their drug in this setting and other earlier cancer settings. Meanwhile in the maintenance treatment of non-small-cell lung cancer, the results of the two studies presented at the weekend are unlikely to convince prescribers. |
Swiss pharmaceutical company Roche and U.S. subsidiary Genentech have published the results of three independent clinical trials following presentations at the 45th Annual Meeting of the American Society of Clinical Oncology (ASCO), held in Orlando, Florida (United States). Those include the full results of the NSABP C-08 study evaluating the benefits of Avastin (bevacizumab) as an adjuvant treatment for colon cancer, the ATLAS study, evaluating the benefits of combination therapy between Avastin and Tarceva (erlotinib) in the maintenance treatment of non-small-cell lung cancer (NSCLC), the SATURN study, evaluating the benefits of Tarceva in the maintenance treatment of NSCLC and the ToGA study evaluating the benefits of Herceptin (trastuzumab) in HER2-positive stomach cancer.
Avastin in Adjuvant Colon Cancer: NSABP C-08 Study
In April 2009, Roche and Genentech announced that Avastin failed to meet its primary endpoint, defined as disease-free survival (DFS) benefits, in the NSABP C-08 (C-08) study (see Switzerland: 22 April 2009: Roche's Avastin Fails to Meet Primary Endpoint in Early-Stage Colorectal Cancer). The randomised Phase III study evaluated the benefits of Avastin in combination with chemotherapy (FOLFOX, 5-fluorouracil, leucovorin and oxaliplatin) over stand-alone chemotherapy in the treatment of colon cancer patients immediately after surgery (adjuvant setting). The full results of the study show that overall, the drug improved DFS by 12%, a figure that was not statistically significant. The two companies nevertheless highlight that in the first year of the clinical trial, adding Avastin to standard six months of chemotherapy, improved DSF by 67%, when compared to stand-alone chemotherapy. Avastin's benefits faded once treatment was halted.
Avastin + Tarceva in the Maintenance Treatment of NSCLC: ATLAS Study
Roche and Genentech have announced that the randomised, double-blind, placebo-controlled ATLAS study met its primary endpoint of extension of progression-free survival (PFS). The study involved 1,160 patients with locally advanced, recurrent or metastatic NSCLC who received four cycles of Avastin alongside chemotherapy, followed by, if their disease did not progress, maintenance therapy with combination treatment between Avastin and Tarceva. The two companies have revealed that median PFS stood at 4.8 months for patients receiving maintenance combination therapy between the two drugs as opposed to 3.7 months for those on Avastin maintenance therapy alone.
Tarceva in the Maintenance Treatment of NSCLC: SATURN Study
Meanwhile, the randomised, double-blind, Phase III SATURN study, which evaluated the benefits of Tarceva-based maintenance therapy in NSCLC patients whose disease was stable after platinum-based chemotherapy, also met its primary endpoint. Indeed, the study showed a significant 41% improvement in PFS in patients on Tarceva maintenance therapy compared to patients on placebo. Interestingly, Tarceva showed greater benefit in the EGFR mutated patient sub-population. In this patient population, maintenance treatment with Tarceva improved survival by 90%.
Herceptin in HER-2 Positive Stomach Cancer: ToGA Study
On a more positive note, Roche and Genentech have announced the full result of the ToGA study, which evaluated the benefits of Herceptin plus chemotherapy in the treatment of HER2-positive stomach cancer patients. Adding Herceptin to chemotherapy extends the prognosis of patients by three months to 13.8 months. The drug's benefits are greater in the HER2-positive patient population where prognosis is extended to an average 16 months.
Outlook and Implications
Although Roche and Genentech have reiterated their confidence in Avastin in the adjuvant colorectal cancer setting, the full results of the C-08 study suggest that their hopes may be slim. One of the implications of the study is that treatment with Avastin should not be discontinued for it to slow down or delay disease progression. There are a number of considerations to take into account with regards to the feasibility of long-term Avastin treatment, one being the cost of therapy and another one being long-term safety. First of all, Genentech has pegged the cost of Avastin in the adjuvant treatment of colorectal cancer at an annual US$52,000. Prolonging treatment for several years would not go unnoticed by cost-conscious health agencies and the drug could face an uphill battle to pass health-economic assessment in this setting. Furthermore, Avastin inhibits vascular formation and the risk associated with long-term use of such agents remains unknown. For Roche and Genentech to demonstrate the benefits of their drug in the longer-term, they would need to produce additional clinical data. Although such studies are under way, according to Dow Jones, their results are not expected before 2017. In addition, the results of the C-08 study raise uncertainty over Avastin's ability to show clinical benefits in early cancers. Indeed the drug is also evaluated as an adjuvant therapy in HER2-positive (BETH study) and HER2-negative (ECOG 5103 and BEATRICE studies) breast cancer as well as in non-squamous, non-small-cell lung cancer (ECOG 1505 study). Disease-free survival is the primary endpoint for all studies except for the lung cancer ECOG 1505 study whose primary endpoint is overall survival. A positive outcome in early breast cancer is also seen as unlikely. Avastin's prospects in early colorectal cancer are unlikely to be salvaged by the AVANT study.
With regards to the ATLAS and SATURN studies, although the results support the use of the drugs in the maintenance therapy of NSCLC, the extent of their benefits may not support wide clinical use. Indeed, the cost of treatment, especially of combination treatment between the two drugs, may not be seen as cost-effective by payors and clinicians. On the other hand, the impressive benefits of Tarceva in the maintenance treatment of EGFR mutated patients is likely to support the drug's use in this patient population and increase demand for EGFR screening. The EGFR mutation is found in about 10% of lung cancer patients. On the other hand, the results of the ToGA study are encouraging for Roche and Genentech as they support an indication extension for Herceptin in the treatment of stomach cancer. Roche estimates that around 900,000 new gastric cancer cases are diagnosed every year, of which 22% would be HER2-positive.