By Kari Bohlke, ScD
Annual meeting brings together cancer experts from around the world.
For thousands of oncology professionals and cancer researchers from around the world, the Annual Meeting of the American Society of Clinical Oncology (ASCO) is an event not to be missed. The meeting offers cutting-edge research findings, a broad range of educational sessions, and a chance to network. The theme of this year’s meeting—held May 31 to June 4 in Chicago—was Building Bridges to Conquer Cancer. The theme highlights the importance of bringing together the many different segments of the oncology community to advance cancer care. Below are a few of the highlights of this year’s meeting.
Continued Progress against Melanoma
Melanoma remains a dangerous type of skin cancer, but significant progress has been made in recent years in the treatment of advanced disease. One important strategy involves drugs that activate the immune system to fight against the cancer. This approach is used by drugs such as Yervoy® (ipilimumab) as well as several promising investigational drugs.
A group of drugs that received attention at this year’s ASCO meeting block a protein known as PD-1. PD-1 inhibits certain types of immune responses, and drugs that block this protein may enhance immune response. In a Phase IB study of patients with advanced melanoma, the investigational, anti–PD-1 drug lambrolizumab produced a treatment response (tumor shrinkage) in 38 percent of patients overall. Among patients who were treated with highest dose of the drug, 52 percent responded to treatment. 1,2
In another Phase I trial of advanced melanoma, the investigational, anti–PD-1 drug nivolumab produced promising results in combination with Yervoy. Among patients who received concurrent treatment with the two drugs, the response rates were 21 percent, 53 percent, and 50 percent, depending on the doses that were used (higher doses produced higher response rates). Thirty-one percent of patients experienced tumor shrinkage of more than 80 percent, and responses tended to occur fairly quickly. 3,4
Although both of these were early-phase studies, the results are quite promising. Lambrolizumab and nivolumab each appear to be active against advanced melanoma.
Sometimes Less Is More
Although many studies report a benefit from adding treatments or using higher doses of treatment, some studies find that less treatment is actually the better choice. A benefit for patients is that less treatment often means fewer side effects.
A Phase III study of two different radiation doses for non–small cell lung cancer illustrated this point. The study enrolled patients with Stage III non–small cell lung cancer and treated them with either the standard dose of 60 gray (Gy) of radiation or a higher dose of 74 Gy. Patients also received chemotherapy with or without Erbitux® (cetuximab). The researchers expected the higher dose of radiation to provide better control of the cancer. The results, however, indicated that the standard dose of radiation produced longer survival, a lower risk of cancer recurrence, and fewer side effects than the higher dose.5
And Sometimes More Is More
Sometimes, of course, more actually is better. A case in point: tamoxifen for the treatment of hormone receptor–positive, early-stage breast cancer. Typically, women are treated with tamoxifen for five years. To assess the effects of extending treatment to 10 years, researchers in the United Kingdom conducted a Phase III trial among nearly 7,000 women. Ten years of treatment resulted in fewer breast cancer recurrences and fewer breast cancer deaths than five years of treatment. Longer treatment did increase the risk of side effects such as endometrial (uterine) cancer, but the researchers concluded that the benefits of longer-term treatment outweighed the risks.6
Tackling Aggressive Thyroid Cancer
Differentiated thyroid cancer is the most common type of thyroid cancer and can often be cured with surgery and radioactive iodine (RAI) treatment. In some cases, however, the cancer is resistant to RAI. Patients with RAI-resistant thyroid cancers have had few effective treatment options.
Nexavar® (sorafenib) is an oral drug that targets certain proteins that contribute to cancer growth. It is used to treat advanced kidney cancer and inoperable liver cancer. To evaluate Nexavar in the treatment of thyroid cancer, researchers conducted a Phase III trial among patients with metastatic, RAI-resistant, differentiated thyroid cancer. Patients were treated with either Nexavar or a placebo. Nexavar almost doubled progression-free survival (survival without a worsening of the cancer): progression-free survival was 10.8 months in the Nexavar group and 5.8 months in the placebo group.7 If Nexavar is approved for this type of cancer, it would be the first new drug in decades to demonstrate effectiveness for this group of patients.
Avastin Not Warranted for Newly Diagnosed Glioblastoma but Improves Cervical Cancer Outcomes
Avastin® (bevacizumab) is a targeted therapy that blocks a protein—vascular endothelial growth factor (VEGF)—that plays a key role in the development of new blood vessels. This deprives the cancer of nutrients and oxygen and inhibits its growth. Avastin is used for the treatment of selected patients with lung cancer, colorectal cancer, kidney cancer, or glioblastoma. In the case of glioblastoma, it is used after other treatments have failed.
Glioblastoma is an aggressive type of brain tumor. Survival tends to be poor even with aggressive treatment, and researchers continue to evaluate new treatment approaches. To evaluate Avastin as part of the initial treatment for glioblastoma, researchers conducted a Phase III clinical trial among newly diagnosed patients. After surgery, patients were treated with chemoradiation (radiation and chemotherapy with Temodar® [temozolomide]) alone or in combination with Avastin. The addition of Avastin increased side effects without improving survival, suggesting that Avastin should not be used for the first-line treatment of glioblastoma.8
In a study of advanced cervical cancer, however, Avastin did provide a benefit. This is important because traditional chemotherapy drugs have limited effectiveness against this disease. In the Phase III trial, conducted by the Gynecologic Oncology Group, women with metastatic or recurrent cervical cancer were treated with chemotherapy alone or in combination with Avastin. The addition of Avastin improved overall survival by roughly four months, from 13.3 months with chemotherapy alone to 17 months with chemotherapy plus Avastin.9
Avoiding Extensive Lymph Node Surgery Reduces Lymphedema Risk
For women with early-stage breast cancer, determining whether the cancer has spread to the axillary (under the arm) lymph nodes is an important part of cancer staging. Evaluation of the axillary nodes often involves a sentinel lymph node biopsy. The sentinel nodes are the first lymph nodes to which cancer is likely to spread. If the sentinel nodes contain cancer, women often undergo more-extensive lymph node surgery (axillary lymph node dissection). A common side effect of axillary lymph node surgery is lymphedema of the arm—swelling of the arm due to an accumulation of lymph fluid.
To evaluate a different approach to treating the axillary lymph nodes, researchers in Europe conducted a Phase III clinical trial among women with early-stage breast cancer and a positive sentinel lymph node (a sentinel lymph node that contained cancer). Women underwent additional lymph node treatment with either surgery or radiation therapy. The results indicated that treatment of the axillary lymph nodes with radiation therapy was effective and had a lower risk of lymphedema. During the first year after treatment, lymphedema developed in 40 percent of the women who had lymph node surgery and 22 percent of the women who had radiation to the lymph nodes. The frequency of lymphedema decreased during subsequent years but continued to favor radiation: at five years 28 percent of the women in the surgery group and 14 percent of women in the radiation group had lymphedema. This study suggests that radiation therapy to the lymph nodes may be an alternative to lymph node surgery for selected women with early-stage breast cancer.10
Maintenance Treatment Provides Ovarian Cancer Benefits
Maintenance treatment refers to treatment that is given after a patient responds to initial treatment but before cancer progression. In a Phase III clinical trial, the targeted drug Votrient® (pazopanib) improved outcomes when used as maintenance therapy among women with advanced ovarian cancer. Votrient is an oral drug that blocks several biological pathways involved in the growth of tumors and new blood vessels. It is currently used for the treatment of advanced kidney cancer and advanced soft-tissue sarcoma.
The study enrolled women with Stage III or Stage IV ovarian cancer, fallopian tube cancer, or primary peritoneal cancer. All of the study participants had undergone surgery and initial chemotherapy. After completion of chemotherapy, study participants received either Votrient or a placebo daily for up to two years. Votrient improved progression-free survival: progression-free survival was 17.9 months among women treated with Votrient and 12.3 months among women treated with placebo. Longer-term follow-up will provide information about the effect of Votrient on overall survival. 11
Genomic Test Also Provides Information about Advanced Breast Cancer
The Oncotype DX® breast cancer test evaluates the activity of certain genes in a sample of tumor tissue. The test provides information about the likelihood of chemotherapy benefit and the risk of cancer recurrence in women with early-stage, hormone receptor–positive, invasive breast cancer. The recurrence score that is generated by the test ranges from 0 to 100, with higher scores indicating a higher risk of recurrence. A version of the test is also available for women with ductal carcinoma in situ (DCIS) of the breast.
To evaluate the Oncotype DX test among women with advanced breast cancer, researchers conducted a study among women with Stage IV breast cancer. Among women with estrogen receptor–positive cancer, those with a higher recurrence score experienced a quicker worsening of the cancer (shorter time to cancer progression). Among women with cancer that was both estrogen receptor–positive and HER2-negative, a higher recurrence score was linked with shorter overall survival. These results suggest that the Oncotype DX breast cancer test provides information about the prognosis of Stage IV, estrogen receptor–positive breast cancer. Additional research would help determine whether women who have a particularly poor prognosis based on the test benefit from more-aggressive treatment.12 _
Oncotype DX Prostate Cancer Test: Using Genomic Testing to Guide Treatment
In findings from another major medication meeting—the 2013 Annual Meeting of the American Urological Association—the Oncotype DX prostate cancer test predicted prostate cancer aggressiveness among men with early-stage prostate cancer. This may help men choose between immediate treatment and active surveillance. Similar to the Oncotype DX breast cancer test, this test assesses the activity of several genes in a sample of tumor tissue.13
References
1. Ribas A, Robert C, Daud A, et al. Clinical efficacy and safety of lambrolizumab (MD-3475, Anti–PD-1 monoclonal antibody) in patients with advanced melanoma. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 9009.
2 . Hamid O, Robert C, Daud A, et al. Safety and tumor responses with lambrolizumab (anti–PD-1) in melanoma. New England Journal of Medicine [early online publication]. June 2, 2013.
3. Wolchok JD, Kluger HM, Callahan MK, et al. Safety and clinical activity of nivolumab (anti–PD-1, BMS-936558, ONO-4538) in combination with ipilimumab in patients (pts) with advanced melanoma (MEL). Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 9012.
4. Wolchok JD, Kluger HM, Callahan MK, et al. Nivolumab plus ipilimumab in advanced melanoma. New England Journal of Medicine [early online publication]. June 2, 2013.
5. Bradley JD, Paulus R, Komaki, R et al. A randomized phase III comparison of standard-dose (60 Gy) versus high-dose (74 Gy) conformal chemoradiotherapy with or without cetuximab for Stage III non–small cell lung cancer: results on radiation dose in RTOG 0617. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 7501.
6. Gray RG, Rea D, Handley K, et al. aTTom: Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 in 6,953 women with early breast cancer. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 5.
7. Brose MS, Nutting C, Jarzab B, et al. Sorafenib in locally advanced or metastatic patients with radioactive iodine-refractory differentiated thyroid cancer: The phase III DECISION trial. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 4.
8. Gilbert MR, Dignam J, Won M, et al. RTOG 0825: Phase III double-blind placebo-controlled trial evaluating bevacizumab (Bev) in patients (Pts) with newly diagnosed glioblastoma (GBM). Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 1.
9. Tewari KS, Sill M, Long HJ III. Incorporation of bevacizumab in the treatment of recurrent and metastatic cervical cancer: a Phase III randomized trial of the Gynecologic Oncology Group. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 3.
10. Rutgers EJ, Donker M, Straver ME, et al. Radiotherapy or surgery of the axilla after a positive sentinel node in breast cancer patients: final analysis of the EORTC AMAROS trial (10981/22023). Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract LBA1001.
11. Du Bois A, Floquet A, Kim JW, et al. Randomized, double-blind, Phase III trial of pazopanib versus placebo in women who have not progressed after first-line chemotherapy for advanced epithelial ovarian, fallopian tube, or primary peritoneal cancer (AEOC): results of an international Intergroup trial (AGO-OVAR16). Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract LBA5503.
12. King TA, Lyman JP, Gonen M, et al. Prognostic impact of the 21-gene recurrence score in patients presenting with Stage IV breast cancer. Paper presented at: 49th Annual Meeting of the American Society of Clinical Oncology; May 31–June 4, 2013; Chicago, IL. Abstract 507.
13. Cooperberg M, Simko J, Falzarano S, et al. Development and validation of the biopsy-based genomic prostate score (GPS) as a predictor of high grade or extracapsular prostate cancer to improve patient selection for active surveillance. Paper presented at: 2013 Annual Meeting of the American Urological Association; May 4-8, 2013; San Diego, CA. Abstract 2131.