The 41st American Society of Clinical Oncology meeting will be held from May 13th to 17th in Orlando, Florida. Few surprises are expected this year with most companies having already released glimpses of trial data that will be presented. While the two biggest stars this year are undoubtedly Avastin and Revlimid, there are many others that are progressing well clinically, and are expected to generate a lot of interest including Tarceva, Herceptin, Sutent and Sorafenib. We have highlighted below some of the drugs that we will be scrutinizing at ASCO this year.

Avastin (Bevacizumab; Genentech)

Avastin has already been approved for colorectal cancer. It is currently in phase III studies for numerous other solid tumors including breast cancer and non-small cell lung cancer, both of which will be presented at ASCO.

Avastin in non-small cell lung cancer
On March 14 (see trial data), Genentech announced that the phase III ECOG 4599 study evaluating Avastin in first-line patients with non-squamous non-small cell lung cancer (NSCLC) met its primary endpoint of improving overall survival. The study showed that Avastin, when combined with paclitaxel and carboplatin, produced a median overall survival of 12.5 months compared to 10.2 months for the paclitaxel/carboplatin control. Detailed results have not yet been released and will be presented at a plenary session at ASCO. Of note is the safety of Avastin in these patients. Avastin has been shown to increase bleeding in the lungs (hemoptysis), particularly in patients with squamous cell NSCLC. Despite the study excluding these patients, it remains to be seen whether the rate of hemoptysis seen in the Avastin-treated group is much higher than that seen in the control group. We believe that if Avastin causes lung bleeding in less than 5% of patients, then it will become the drug treatment of choice in front-line non-squamous NSCLC. A higher rate of hemoptysis will likely dampen the enthusiasm surrounding Avastin for NSCLC.

Avastin in breast cancer
Genentech announced on April 15th (see data) that the pivotal phase III study, ECOG 2100, evaluating Avastin in front-line metastatic breast cancer patients also met its primary endpoint. The study showed that Avastin, in combination with paclitaxel, improved progression-free survival compared to paclitaxel alone. This announcement came as a welcomed surprise given that Avastin previously failed to demonstrate a benefit in second-line metastatic breast cancer (when combined with Xeloda (Capecitabine; Roche). The results of this study were submitted as a late-breaker abstract and will form the basis of Avastin’s registration in front-line metastatic breast cancer.

Herceptin (Trastuzumab; Genentech)

Herceptin has been approved as a front-line treatment for patients with HER-2 positive metastatic breast cancer. Herceptin is currently been evaluated in earlier breast cancer in the adjuvant setting. On April 25 (see data), Genentech announced that the 2 phase III studies of Herceptin in the adjuvant setting were halted early due to improvements in both the primary and secondary endpoints of the trials. The interim analyses on 3,300 women with HER-2 positive breast cancer demonstrated that the addition of Herceptin to chemotherapy improved both progression-free survival and overall survival. Detailed interim data from these studies will be presented at ASCO. Results from these studies should provide enough evidence to warrant the use of Herceptin earlier in the treatment of HER-2 positive breast cancer.

Tarceva (Erlotinib; OSI and Genentech)

Tarceva in pancreatic cancer
OSI will present data from the pivotal phase III study of Tarceva in patients with advanced pancreatic cancer, which was previously released. The study showed that the addition of Tarceva to Gemzar (gemcitabine) improved overall survival from 5.9 months with Gemzar alone to 6.4 months. While the results have been released previously, a supplemental NDA was submitted to the FDA on May 2, 2005 and the ASCO forum will help promote Tarceva to oncologists despite the modest improvement in survival in pancreatic cancer.

Tarceva in non-small cell lung cancer
Tarceva has already been approved for second-line NSCLC based on positive interim data from the phase III BR.21 study, which was presented last year at ASCO. Full final data is expected at this year’s ASCO. While the final results will be interesting, we are more anxious to see data from the phase II study of Tarceva as a stand alone treatment in front-line NSCLC.

Results from a phase I/II study of Tarceva in combination with Avastin in second-line NSCLC is also expected at ASCO. It will be interesting to see how the combination of the drugs will be tolerated and more importantly, whether the combination of these two targeted therapies has additional benefits over each drug given alone.

Sorafenib (BAY 43-9006; Onyx and Bayer)

Sorafenib is a tyrosine kinase inhibitor that inhibits the VEGF and PDGF pathways. Sorafenib is unique in that it also inhibits the RAF kinase pathway, which has been shown to be important in promoting cell proliferation and metastasis. On March 21 (see data), Onyx and Bayer announced that the pivotal phase III study of Sorafenib in advanced renal cell cancer (RCC) met its primary endpoint of progression-free survival. While the study is ongoing to determine the effect of the drug on overall patient survival, the companies are currently preparing an NDA for Sorafenib based on this progression-free survival data. Full interim data from this study will be given as an oral presentation at ASCO and it will be interesting to see how Sorafenib and Sutent will compete with each other in the RCC market.

Sutent (SU-11248; Pfizer)

Sorafenib’s main competitor for RCC is Sutent, another tyrosine kinase inhibitor that also inhibits the VEGF and PDGF pathways. Unlike Sorafenib, Sutent does not inhibit RAF kinases. Sutent is currently in phase III studies for RCC. In late 2004, Pfizer announced that in a phase II study in second-line RCC, Sutent significantly increased the objective response rate and the time to disease progression. These results will be presented at ASCO.

While Sorafenib will probably have first-to-market advantage over Sutent for RCC, Sutent will also likely gain FDA approval in early 2006 for gastrointestinal stromal tumors (GIST). On February 8, Pfizer announced that the pivotal phase III study of Sutent in Gleevec (imatinib) resistant GIST was halted early due to a recommendation by the independent data monitoring committee. The committee decided that Sutent demonstrated sufficient efficacy (time to disease progression) and safety to discontinue the trial and to allow patients on the placebo arm to be given the drug.

This positive interim analysis, which will support an NDA filing expected in the second half of 2005, will be presented at ASCO. With both Sorafenib and Sutent likely to receive FDA approval in early 2006, it will be interesting to see how the RCC market plays out, and whether Sutent will be used off-label in RCC once it gains approval for GIST.

Provenge (APC 8015; Dendreon)

Provenge is an immunotherapy that is being evaluated in 3 phase III studies in androgen-independent (hormone-refractory) prostate cancer (AIPC). The final data from the first phase III study of Provenge in AIPC, study D9901, will be presented at ASCO. While the results from this study were previously presented at the multidisciplinary prostate cancer symposium in February, presentation at ASCO will help generate interest in Provenge. In study D9901, Provenge treatment improved survival in AIPC patients of all Gleason scores. This comes as a surprise as early interim analyses of Provenge showed that Provenge was only beneficial in patients with Gleason scores of 7 or less. This new final analyses forms the basis of the Dendreon’s decision to amend the protocol of the pivotal phase III study, D9902B, to include patients with Gleason scores of 8 or higher, which were previously excluded. While the amendment will probably delay the registration of Provenge, it opens the market considerably and may benefit Dendreon in the long run.

Revlimid (Lenalidomide; Celgene)

Aside from Avastin, the biggest star at ASCO this year will be Revlimid. Revlimid is a second-generation thalidomide (Thalomid; Celgene) that was designed to be more potent and less toxic than thalidomide. While ASCO does not typically showcase hematological cancers, there will be 3 presentations of Revlimid in hematological cancers at this year’s ASCO, two of which will be highly anticipated oral presentations.

Revlimid in myelodysplastic syndrome (MDS)
The first presentation is results from the phase II study, MDS-003, of Revlimid in 5q minus myelodysplastic syndrome (MDS). While Revlimid is being evaluated in 5q non-deletion and 5q-deletion patients, the results from the 5q-deletion patients have been most compelling. Interim data were presented at the American Society for Hematology in December 2004, which demonstrated that Revlimid promoted independence from blood transfusions (the standard of care for these patients) in two-thirds of 5q minus patients. Not only did Revlimid promote transfusion-independence, it normalized bone marrow histology in a third of the patients. These results are highly encouraging and we look forward to the presentation of final data at ASCO. Of special interest is the safety profile of Revlimid, which has caused some concern as a few deaths have been noted in the Revlimid treated group. This presentation should generate a lot of interest in Revlimid and should the safety profile be acceptable, we expect Revlimid to dominate the 5q deletion MDS market. An NDA was filed in April for Revlimid in MDS and approval is expected in October 2005.

Revlimid in multiple myeloma
The second presentation of Revlimid will be for the treatment of relapsed/refractory multiple myeloma (MM). Revlimid is being investigated in two pivotal phase III studies under a SPA and it was announced on March 7 (see data) that both studies were halted early due to recommendation by the independent data monitoring committee. The committee found that Revlimid, in combination with dexamethasone, resulted in a statistically significant improvement in time to disease progression compared to dexamethasone alone. Full details from these studies will be presented at ASCO, and as noted above, we will be especially interested in the toxicity profile of Revlimid in these patients. A supplemental NDA for Revlimid in multiple myeloma is expected in the fall of 2005, which makes it likely that Revlimid will gain FDA approval for both MDS and MM by early 2006.

Drugs in early development

Perifosine (KRX-0401; AEterna Zentaris and Keryx)

Perifosine is an AKT inhibitor in phase II studies for a number of solid tumors. A poster presentation in androgen-dependent (hormone-sensitive) prostate cancer will be presented at ASCO. As yet, there are no AKT inhibitors on the market and this presentation will be interesting to determine the value of AKT inhibition relative to the inhibition of other kinases.

Telcyta (TLK 286; Telik)

While Telcyta is being evaluated in phase III studies in second-line NSCLC, interim data from two early studies of Telcyta in front-line NSCLC will be presented at ASCO. The first study is a phase I/II study evaluating Telcyta in combination with cisplatin and while the second study is phase II study evaluating Telcyta in combination with carboplatin and paclitaxel.

Vitaxin (MEDI-522; Eli Lilly and MedImmune)

Vitaxin is a monoclonal antibody that binds to alpha-V-beta-3 integrin, which is found on a number of cells, such as macrophages and osteoclasts, as well as new blood vessels. While the trials in psoriasis and rheumatoid arthritis have been discontinued due to lack of efficacy, phase II studies are ongoing for prostate cancer and melanoma. Preliminary results from the metastatic melanoma trial in which patients will be given Vitaxin with or without dacarbazine (DTIC) will be presented at ASCO. We will be interested to see if Vitaxin can show efficacy for this difficult to treat disease.