ASCO 2011

Annual meeting brings together cancer experts from around the world.

Kari Bohlke, ScD

The 2011 Annual Meeting of the American Society of Clinical Oncology (ASCO), held June 3 to 7 in Chicago, brought together an estimated 30,000 oncology specialists. The studies presented at the meeting addressed topics ranging from prevention and early detection through treatment and survivorship.

Progress against Melanoma

New treatments are finally making inroads against advanced melanoma—a type of cancer that historically has been difficult to treat.

Yervoy™ (ipilimumab) was approved in March 2011 for the treatment of melanoma that has spread to other sites or cannot be surgically removed. The drug targets a molecule known as CTLA4, which is found on the surface of T-cells and is thought to inhibit immune responses. By targeting this molecule, Yervoy may enhance the immune system’s response to tumor cells.

To evaluate the combination of Yervoy and the chemotherapy drug dacarbazine for the initial (first-line) treatment of advanced melanoma, researchers conducted a Phase III clinical trial among 502 patients with Stage III or Stage IV melanoma that could not be surgically removed.1 Study participants were treated with dacarbazine alone or in combination with Yervoy.

Three-year overall survival was 20.8 percent among patients treated with chemotherapy plus Yervoy compared with 12.2 percent among patients treated with chemotherapy alone.

Serious side effects were more common in the Yervoy group: grade 3 or grade 4 side effects occurred in 56 percent of patients treated with Yervoy and chemotherapy and in 27 percent of patients treated with chemotherapy alone.

Another drug that is producing promising results is vemurafenib, an investigational drug that targets a specific mutation (V600E) in the BRAF gene. Approximately half of all melanomas carry this mutation.

To evaluate vemurafenib in the treatment of advanced melanoma, researchers conducted a Phase III clinical trial among 675 patients with previously untreated, inoperable, Stage IIIC or Stage IV melanoma.2 The study was restricted to patients with a V600E mutation. Study participants were treated with either vemurafenib or the chemotherapy drug dacarbazine.

Compared with patients in the chemotherapy group, patients in the vemurafenib group had a 63 percent reduction in risk of death and a 74 percent reduction in risk of melanoma progression.

Tumor shrinkage occurred in 48.4 percent of patients in the vemurafenib group and 5.5 percent of patients in the dacarbazine group.

Less than 10 percent of patients in the vemurafenib group experienced severe side effects (grade 3 or worse). The most common side effects of vemurafenib were skin rashes, sensitivity to light, and joint pain.

Combinations of targeted therapies may further improve outcomes, making this a very exciting time for melanoma research and treatment.

Avastin Shows Benefit in Ovarian Cancer

According to two studies presented at ASCO, the addition of the targeted drug Avastin® (bevacizumab) to chemotherapy may improve outcomes among women with newly diagnosed or recurrent ovarian cancer.

Avastin is a targeted therapy that blocks a protein known as vascular endothelial growth factor (VEGF). VEGF plays a key role in the development of new blood vessels. By blocking VEGF, Avastin deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin has been approved for the treatment of selected patients with breast cancer, lung cancer, colorectal cancer, kidney cancer, or glioblastoma.

To evaluate Avastin among women with recurrent ovarian, peritoneal, or fallopian tube cancer, researchers conducted a Phase III clinical trial (the OCEANS study) among 484 patients with platinum-sensitive disease.3 Study participants were treated with chemotherapy (carboplatin and gemcitabine) in combination with either Avastin or a placebo. After chemotherapy was completed, patients continued to receive Avastin or a placebo until cancer progression.

Progression-free survival was 12.4 months in the Avastin group and 8.4 months in the group that received chemotherapy alone.

In a second study, researchers evaluated Avastin in the treatment of newly diagnosed ovarian cancer that had a high risk of recurrence.4 The Phase III ICON7 study enrolled 1,528 women with high-risk or advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer. Study participants were treated with chemotherapy with or without Avastin. Women in the Avastin group continued Avastin treatment after chemotherapy was completed.

Overall, the Avastin group had a 15 percent reduction in risk of death (178 deaths in the Avastin group versus 200 in the chemotherapy-alone group). This difference between study groups did not meet the criteria for statistical significance, suggesting that it could have occurred by chance alone.

In the subgroup of women at highest risk of recurrence, Avastin reduced the risk of death by 36 percent (79 deaths in the Avastin group versus 109 in the chemotherapy-alone group). This result was statistically significant, which suggests that it’s unlikely to have occurred by chance alone.

These results suggest that Avastin may improve outcomes for certain groups of ovarian cancer patients.

Aromasin Reduces Breast Cancer Risk in High-Risk Women

In a Phase III clinical trial, the aromatase inhibitor Aromasin® (exemestane) reduced the risk of breast cancer in postmenopausal women at increased risk of the disease.

Aromatase inhibitors are drugs that block the production of estrogen in postmenopausal women. These drugs are commonly used in the treatment of hormone receptor–positive breast cancer but may also have a role in breast cancer prevention. Aromatase inhibitors include Aromasin, Arimidex® (anastrozole), and Femara® (letrozole).

To evaluate Aromasin for breast cancer prevention in high-risk women, researchers conducted a Phase III trial among 4,560 postmenopausal women.5 Study participants received either Aromasin or a placebo and have now been followed for an average of three years.

Risk of invasive breast cancer was 65 percent lower among women in the Aromasin group than among women in the placebo group. There were 11 invasive breast cancers in the Aromasin group and 32 invasive breast cancers in the placebo group.

Symptoms such as hot flashes, fatigue, sweating, insomnia, and joint pain were common among all study participants but slightly more so among women treated with Aromasin.

These results suggest that Aromasin may be safe and effective when used to reduce the risk of breast cancer in high-risk women. Drugs that have previously been approved for this purpose are tamoxifen and Evista® (raloxifene).

Cabozantinib Shows Promise against Bone Metastases

The investigational drug cabozantinib is showing promise against several types of advanced cancer and may also reduce or eliminate bone metastases (cancer that has spread to the bone) in some patients.

Several types of cancer—including cancers of the prostate, lung, and breast—have a tendency to spread to the bone. Bone metastases can lead to serious problems such as fracture and spinal cord compression and may require treatment with surgery or radiation therapy.

Cabozantinib is an investigational drug that targets two proteins—MET and VEGFR2—that play a role in the development and the progression of many types of cancer.

To evaluate cabozantinib in the treatment of advanced cancer, researchers conducted a Phase II clinical trial among 398 patients.6 The nine types of cancer included in the study were breast, stomach/gastroesophageal junction, non–small cell lung, ovarian, pancreatic, hormone-refractory prostate, small cell lung, liver, and melanoma. At the start of the study, 39 percent of the patients had bone metastases.

Patients were initially treated with 12 weeks of cabozantinib. After 12 weeks patients who had a partial response to treatment (a reduction in detectable cancer) remained on cabozantinib, patients with stable disease (no significant change in the cancer) were randomly assigned to either continue with cabozantinib or to take a placebo, and patients with progressive (worsening) cancer were withdrawn from the study.

By the twelfth week, 9 percent of patients responded to treatment.

For some types of cancer, cabozantinib produced high disease control rates (defined as either a reduction in cancer or stable disease). The disease control rates were 76 percent for liver cancer, 71 percent for prostate cancer, and 58 percent for ovarian cancer.

Among the 68 patients with bone metastases, 59 had partial or complete disappearance of the cancer on bone scans, often accompanied by significant pain relief. A majority of these patients had hormone-refractory prostate cancer, but patients with breast cancer and melanoma also experience a disappearance of bone metastases. The researchers had not expected this result.

The most common side effects were fatigue and hand-foot syndrome (pain, swelling, numbness, tingling, or redness of the hands or feet).

If these results are confirmed by additional studies, cabozantinib could provide an important new treatment option for several types of cancer.

Screening with CA-125 and Ultrasound Does Not Reduce Ovarian Cancer Mortality

Roughly 70 percent of ovarian cancers are diagnosed at an advanced stage, highlighting the importance of developing an ovarian cancer screening strategy that accurately detects cancer at an early, more-treatable stage. Potential ovarian cancer screening tests include the CA-125 blood test and transvaginal ultrasound. Levels of the CA-125 protein tend to increase in the bloodstream during ovarian cancer development but can also rise as a result of other conditions. These tests have not been recommended for routine screening of asymptomatic, average-risk women because of lack of evidence that screening provides a benefit (i.e., reduces ovarian cancer mortality).

To further assess CA-125 and transvaginal ultrasound as ovarian cancer screening tests, researchers evaluated information from the Prostate, Lung, Colorectal, and Ovarian (PLCO) cancer screening trial.7 The trial assigned more than 78,000 women between the ages of 55 and 74 to annual ovarian cancer screening or usual care.

The number of ovarian cancer deaths was similar in the two study groups: 118 in the screening group versus 100 in the usual-care group. The number of deaths from other causes was also similar in the two groups.

3,285 women in the screening group had a false-positive result (a screening test that suggested cancer when none was present). More than 1,000 of these women underwent surgery, and 163 had at least one serious complication.

These results suggest that screening for ovarian cancer with a CA-125 blood test and transvaginal ultrasound does not reduce the risk of death from ovarian cancer and can cause harm when false-positive test results lead to unnecessary surgery.

The findings of this study do not apply to women who are experiencing potential symptoms of ovarian cancer such as persistent bloating, pelvic or abdominal pain, difficulty eating or feeling full quickly, and urinary frequency or urgency. Women should discuss these and other symptoms with their healthcare provider.

Women at high risk of ovarian cancer as a result of their personal or family medical history should also talk with their healthcare provider. There are strategies available to help high-risk women reduce or manage their cancer risk.

Three Years of Treatment with Gleevec Improves Survival with Gastrointestinal Stromal Tumors

Treatment with Gleevec® (imatinib) for three years following surgery significantly improves survival compared with the standard one-year therapy for patients with gastrointestinal stromal tumors (GIST).

GIST is a type of soft-tissue sarcoma that develops in the stomach, the small intestine, or other parts of the gastrointestinal tract. Treatment of early GIST often involves surgery followed by treatment with Gleevec. Gleevec is a type of targeted therapy that inhibits a specific protein that is overactive in the majority of GIST cells.

Researchers from Scandinavia recently conducted a clinical study (the Scandinavian Sarcoma Group XVIII/AIO trial) to explore the effectiveness of longer therapy with Gleevec among patients with GIST.8 The study included 400 patients with early GIST who were at a high risk of experiencing a recurrence. Following surgery one group was treated with Gleevec for three years while the other group was treated with Gleevec for one year.

Survival was significantly improved for the group of patients treated with Gleevec for 3 years compared with those treated for only 1 year. At 5 years survival was 92 percent for the 3-year group and 81.7 percent for the 1-year group.

Survival with no evidence of cancer recurrence (recurrence-free survival) was also improved in the group of patients treated with Gleevec for 3 years. Three years following surgery, recurrence-free survival was 65.5 percent in the 3-year group compared with 48 percent in the 1-year group.

By the end of therapy with Gleevec, 14 percent of the group treated for 3 years and 8 percent of the group treated for 1 year had discontinued therapy due to side effects.

These results suggest that longer treatment with Gleevec can improve GIST outcomes. Research on the optimal duration of Gleevec continues.

Oncotype DX Identifies Stage II Colon Cancer with Higher Risk of Recurrence

Among patients with Stage II colon cancer, the Oncotype DX® colon cancer test provides information about the risk of cancer recurrence and may help guide treatment decisions.

Stage II colon cancer refers to cancer that extends through the wall of the colon but has not invaded lymph nodes or spread to distant parts of the body. Many patients with this stage of disease have good outcomes with surgery alone, and routine adjuvant (post-surgery) chemotherapy is not currently recommended for Stage II colon cancer. Chemotherapy may, however, be considered for Stage II patients with a higher risk of cancer recurrence.

The Oncotype DX colon cancer test—which is similar to a test that is commonly used for patients with early-stage breast cancer—estimates the risk of cancer recurrence by evaluating the activity of certain genes in a sample of tumor tissue. In the current study, the Oncotype DX recurrence score and other factors were evaluated among patients with Stage II colon cancer who participated in the CALGB 9581 study.9

Even after accounting for such factors as stage, grade, number of lymph nodes examined, and mismatch repair (MMR) protein status, the recurrence score was a significant predictor of recurrence risk.

The researchers also evaluated the recurrence score in a subset of patients for whom traditional factors such as grade do not provide prognostic information (patients with T3 Stage II cancer and intact MMR protein function). Once again the recurrence score was able to identify patients who had a high risk of cancer recurrence: five-year risk of recurrence was more than 20 percent among patients with the highest recurrence scores.

These results confirm that the Oncotype DX colon cancer test provides new information about recurrence risk in patients with Stage II colon cancer. The test may help guide treatment decisions by identifying patients with more aggressive disease.

News coverage provided by Kari Bohlke, ScD, and Jenny Maxon, RN.

references

1. Wolchok JD, Thomas L, Bondarenko IN, et al. Phase 3 randomized study of ipilimumab (IPI) plus dacarbazine (DTIC) vs DTIC alone as first line treatment in patients with unresectable stage III or IV melanoma. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA5.

2. Chapman PB, Hauschild A, Robert C, et al. Phase III randomized, open-label, multicenter trial (BRIM3) comparing BRAF inhibitor vemurafenib with dacarbazine (DTIC) in patients with V600E BRAF-mutated melanoma. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA4.

3. Aghajanian C, Finkler NJ, Rutherford T, et al. OCEANS: A randomized, doubled-blinded, placebo-controlled, Phase III trial of chemotherapy with or without bevacizumab (BEV) in patients with platinum-sensitive recurrent epithelial ovarian (EOC), primary peritoneal (PPC), or fallopian tube cancer (FTC). Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA5007.

4. Kristensen G, Perren T, Qian W, et al. Result of interim analysis of overall survival in the GCIG ICON7 Phase III randomised trial of bevacizumab in women with newly diagnosed ovarian cancer. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA5006.

5. Goss PE, Ingle JN, Ales-Martinez J, et al. NCIC CTG MAP.3: A Phase III placebo-controlled breast cancer prevention trial of exemestane in postmenopausal women at risk for breast cancer. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA504.

6. Gordon MS, Vogelzang NJ, Schoffski P, et al. Cabozantinib (XL184) has activity in both soft tissue and bone: results of a phase II randomized discontinuation trial (RDT) in patients (pts) w/ advanced solid tumors. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3010.

7. Buys SS, Partridge E, Black A, et al. Effect of screening on ovarian cancer mortality in the prostate, lung, colorectal and ovarian (PLCO) cancer randomized screening trial. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 5001.

8. Joensuu H, Eriksson M, Hatrmann J, et al. Twelve versus 36 months of adjuvant imatinib (IM) as treatment of operable GIST with a high risk of recurrence: final results of a randomized trial (SSGXVIII/AIO). Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract LBA1.

9. Venook AP, Niedzwiecki D, Lopatin M, et al. Validation of a 12-gene colon cancer recurrence score (RS) in patients (pts) with Stage II colon cancer (CC) from CALGB 9581. Paper presented at: 47th Annual Meeting of the American Society of Clinical Oncology; June 3-7, 2011; Chicago, IL. Abstract 3518.