Major Advances in Clinical Cancer Research in 2009: A Report From ASCO

Zosia Chustecka

November 17, 2009

November 17, 2009 — This year's annual report on clinical cancer advances from the America Society of Clinical Oncology (ASCO) highlights 15 studies described as "major advances" and 51 studies considered to be "notable advances."

Each of the studies highlighted has "significantly altered the way a cancer is understood or had an important impact on patients care," the report notes.

"These continuing research advances should encourage people with cancer and those who care for them," said ASCO president Douglas W. Blayney, MD. "As this report demonstrates, investment in clinical cancer research is paying off."

The report was developed by 18 leading oncologists who selected the studies from a review of the scientific literature and presentations made at major scientific meetings over a 1-year period (October 2008 to September 2009). The 2 main conferences were the ASCO 45th Annual Meeting (ASCO 2009) held in May and June 2009 and the American Society of Hematology 50th Annual Meeting (ASH 2008) held in December 2008.

Most of these studies were reported by Medscape Oncology.

Some of the Major Advances in Cancer

First standard of care for biliary tract cancer. A combination of gemcitabine and cisplatin was shown to improve survival over gemcitabine alone (Valle JW et al. ASCO 2009: Abstract 4503).

First effective immunotherapy for neuroblastoma. The product is an antibody-based immunotherapy (chimeric anti-GD2 antibody ch14.18) that targets a glycolipid (GD2) on neuroblastoma cells. A phase 3 trial showed a reduction in the risk for relapse and an improvement in overall survival at 2 years in children with high-risk neuroblastoma (Yu AL et al. ASCO 2009: Abstract 10067z).

Trastuzumab improves survival in human epidermal growth-factor receptor 2 (HER2)-positive gastric cancer. The phase 3 ToGA study reports significantly improved survival in these patients (van Cutsem E et al. ASCO 2009: Abstract LBA4509).

Cetuximab added to chemotherapy extends survival in advanced head and neck cancer. Patients in the phase 3 EXTREME study showed a significant improvement when cetuximab was added to cisplatin-based chemotherapy (Vermorken JB et al. N Engl J Med. 2008;359:1116-1127).

Radiation reduces risk for metastasis and increases survival after prostatectomy. The report describes this study as practice changing. Results after a median follow-up of nearly 13 years showed that radiation after radical prostatectomy reduces the risk for metastasis by 29% and improves survival by 28% (Thompson IM et al. J Urol. 2009;181:956-962).

Prostate-specific antigen (PSA) testing has minimal effect on reducing prostate cancer mortality. The results from 2 large screening trials suggest that routine measurement of PSA has a small, if any, effect on reducing the risk of dying from prostate cancer, and has likely led to the overdiagnosis and treatment of disease that is slow-growing and nonlethal. These findings will influence patient–doctor communication about the risk and benefits of PSA testing, the report notes (Andriole GL et al. N Engl J Med. 2009;360:1310-1319; Schroder FH et al. N Engl J Med. 2009;360:1320-1328).

Maintenance pemetrexed therapy improves survival in lung cancer. The survival benefit was seen in patients with stage 3B or 4 nonsquamous nonsmall-cell lung cancer (NSCLC), including adenocarcinoma and large cell carcinoma, in a phase 3 trial. These results have changed the standard of care for patients with advanced NSCLC, says the report (Belani CP et al. ASCO 2009: Abstract CRA8000).

Tumor mutation predicts response to gefitinib in lung cancer. Data from the IPASS study showed that Asian patients with NSCLC with mutations in the epidermal growth-factor receptor (EGFR) gene who were nonsmokers or light smokers had a significantly better initial response to gefitinib and fared better on gefitinib than on conventional chemotherapy (with carboplatin and paclitaxel) (Fukuoka M et al. N Engl J Med. 2009;361:947-957).

Combination chemotherapy superior to capecitabine alone for breast cancer in older women. These results come from the Cancer and Leukemia Group B trial, which showed that standard chemotherapy halved the risk for death and relapse (Muss HB et al. N Engl J Med. 2009;360:2055-2065).

Everolimus and bevacizumab approved for renal cell carcinoma. Everolimus showed improvement in progression-free survival in patients with metastatic renal cell carcinoma that progressed despite treatment with sunitinib and/or sorafenib in a phase 3 trial (Motzer RJ et al. Lancet 2008;372:449-456). Bevacizumab together with interferon improved progression-free survival in metastatic renal cell carcinoma in 2 phase 3 studies (Escudier BJ et al. ASCO 2009: 5020. Rini BI et al. ASCO 2009: LBA5019).

Bevacizumab approved for advanced glioblastoma. Bevacizumab is the first new drug for this disease in a decade. The approval was based on 2 studies, 1 of which was a phase 2 study that showed an improvement in progression-free and overall survival compared with historic controls in patients who had received previous treatment with temozolomide and radiation (Kreisl TN et al. J Clin Oncol 2009;27:740-745).

Bevacizumab does not reduce recurrence risk for early-stage colon cancer. These results come from the National Surgical Adjuvant Breast and Bowel Project, and show that adding bevacizumab to standard adjuvant chemotherapy (5-flurorouracil, leucovorin and oxaliplatin; known as FOLFOX) did not improve disease-free survival in stage 2 and 3 colon cancer (Womark N et al. ASCO 2009: Abstract LBA4).

Frequent CA125 testing to monitor for recurrence of ovarian cancer unnecessary. These findings could change the way that women are monitored after achieving remission from ovarian cancer, the report notes, because they suggest that second-line treatment can be safely delayed until symptoms of relapse develop, which could spare women the anxiety associated with frequent testing (Rustin GJ et al. ASCO 2009: Abstract 1).

HPV vaccine effective in older women (24 to 45 years). The human papillomavirus (HPV) vaccine (Gardasil) is currently approved for use in women 9 to 26 years of age; this study showed that older women who have not been infected might benefit from the same protection (Munoz N et al. Lancet. 2009;373:1949-1957).

Some of the Notable Advances in Cancer

5-alpha reductase inhibitors reduce risk for prostate cancer. Their use was recommended in guidelines released jointly by ASCO and the American Urological Association (J Clin Oncol. 2009;27:1502-1516).

Circulating tumor cell test approved for predicting prostate cancer outcomes. The test, CellSearch, can be used to monitor treatment in men with advanced prostate cancer, and results from 1 trial showed that it predicted survival more accurately than PSA testing (de Bono JS et al. Clin Cancer Res. 2008;14:6302-6309).

Prophylactic surgery reduces risk for breast and ovarian cancer in women with BRCA gene mutations. A pooled analysis of 10 studies confirmed the risk reduction from salpingo-oophorectomy in BRCA1 and BRCA2 mutation carriers. Such women have a lifetime risk of up to 84% for breast cancer and up to 46% for ovarian and fallopian tube cancers. Surgical removal of the ovaries and fallopian tubes reduced the risk for breast cancer by 51% and the risk for ovarian and fallopian tube cancers by 79% (Rebbeck TR et al. J Natl Cancer Inst. 2009;101:80-87).

Importance of ALK gene in lung cancer. A small phase 1 study found that patients with NSCLC tumors that contain a somatic genetic change — the translocation of the EML4 and ALK genes — had a significant response to treatment with PF-02341066, a targeted oral drug that inhibits ALK receptor kinase. Larger trials are needed, the report notes, but none of these patients had EGFR mutations and therefore represent a new group of lung cancer patients who have a quick and substantial improvement after taking an oral kinase inhibitor (Kwak EL et al. ASCO 2009: Abstract 3509).

Genetics of glioblastoma characterized by The Cancer Genome Atlas. Researchers identified several genetic mutations that characterize glioblastoma, which could be of potential use in developing targeted therapy (Nature. 2008;455:1061-1068).

Therapeutic vaccine extends survival in glioblastoma in a phase 2 study. The vaccine, known as PEPvIII-KLH, targets a variant of EGFR, and was used together with temozolomide and radiation (Sampson JH et al. ASCO 2009: Abstract 2034).

New gene assay predicts colon cancer recurrence risk. The Oncotype DX assay, similar to a test already marketed for breast cancer, generates a "recurrence score" that can be used along with other pathologic measures to determine whether colon cancer is likely to recur, which in turn can guide the decision of whether to use adjuvant chemotherapy (Kerr D et al. ASCO 2009: Abstract 4000).

BRAF mutations predict worse outcome in metastatic colon cancer. The report notes that the BRAF gene might eventually prove as useful as the KRAS gene in predicting which patients are most likely to respond to EGFR inhibitors, such as cetuximab (Erbitux) and panitumumab (Vectibix) (Di Nicolantonio F et al. J Clin Oncol 2008;26:5705-5712).

Gefitinib not superior to methotrexate for improving survival in recurrent head and neck cancer. Many of these cancers overproduce EGFRs, but the EGFR inhibitor gefitinib did not improve survival over methotrexate, the historic standard therapy (Stewart JSW et al. J Clin Oncol. 2009;27:1864-1871).

Oral HPV test shows promise in screening for certain head and neck cancers. The test consists of a saline oral rinse that captures naturally shed oral mucosal cells, and uses a DNA amplification strategy to test for HPV 16 (Agrawal Y et al. Clin Cancer Res. 2008;14:7143-7150).

Induction chemotherapy in larynx preservation during treatment for larynx and hypopharynx cancer. Two new studies were reported. One showed that induction chemotherapy (with cisplatin and 5-fluorouracil) followed by definitive radiation therapy gave similar results to concurrent chemoradiation with lower doses of chemotherapy (Lefebvre JL et al. J Natl Cancer Inst. 2009;101:142-152). The other study showed that a chemotherapy regimen of cisplatin, 5-flurouracil, and a taxane is superior to standard chemotherapy with cisplatin and 5-flurouracil (Pointreau Y et al. J Natl Cancer Inst. 2009;101:498-506).

Reradiation reduces local recurrence risk but does not improve survival in head and neck cancer. The finding comes from a phase 3 trial in which patients with head and neck cancer who developed recurrent disease or a second primary cancer in an area that had been previously irradiated were treated with salvage surgery, and then half underwent chemo-reirradiation (Janot F et al. J Clin Oncol. 2008;26:5518-5523).

Melanoma incidence rising in the United States. The incidence has risen sharply and cannot be attributed to increased screening alone (Linos E et al. J Invest Derm. 2009;129:1666-1674).

Vaccine effective in melanoma. The experimental therapeutic vaccine contains part of the gp100 protein, an antigen found on melanoma cells but not on healthy cells, and stimulates T-cells to attack melanoma cells. A phase 3 trial showed that adding the vaccine to standard therapy with interleukin-2 more than doubled the response rate, and increased both progression-free and overall survival (Schwartzentruber DJ et al ASCO 2009: Abstract CRA9011).

Novel drug PLX4032 effective in melanoma with BRAF mutations. The drug is an oral inhibitor of BRAF kinase, and the data come from a small phase 1 study (Flaherty K et al. ASCO 2009: Abstract 9000).

BiovaxID personalized vaccine prolongs disease-free survival for follicular lymphoma. The vaccine is individually manufactured for each patient. The report notes that more studies are needed to test the vaccine in patients who are taking rituximab, which was not a standard of care when the trial started 8 years ago. (Schuster SJ et al. ASCO 2009: Abstract 2).

Pralatrexate shown to shrink T-cell lymphoma in phase 2 PROPEL study. The drug is an inhibitor of RFC-1, a protein overexpressed in T-cell lymphoma cells, and has just been granted accelerated approval by the US Food and Drug Administration on the basis of this trial (O'Connor OA et al, ASH 2008: Abstract 261).

Fostamatinib shows activity in lymphoma and chronic leukemia. Promising early-stage (phase 1) studies showed that this investigational drug, an inhibitor of Syk kinase, is one of the first targeted oral agents to show activity in lymphomas. All current treatments are given intravenously, the report notes. (Friedburg JW et al. ASH 2008: Abstract 3)

Computer-aided detection system enhances accuracy of single reading of mammograms. Previous studies have shown that the interpretation of mammograms by 2 specialists (double reading) increases the rate of breast cancer detection about 4-fold, compared with single reading, but shortages of specialists mean that it is not always possible. This British study showed that single reading using a computer-aided detection system (ImageChecker DMax) gave a detection rate similar to that with double reading, and is an effective substitute (Gilbert FJ et al. N Engl J Med. 2008;359:1675-1684).

PARP inhibitors show promise in hard-to-treat breast cancers. These include triple negative and BRCA1/2-deficient breast cancers. Results from phase 2 trials with 2 experimental products, BSI-201 and olaparib, have been reported (O'Shaughnessy J et al and Tutt A et al. ASCO 2009: Abstracts 3 and CRA501).

Long Road Ahead

The report also highlights advances in cancer disparities and in quality of life and quality of cancer care. It makes recommendations for improving clinical cancer research in the future, the most prominent of which is a call for increased federal funding.

"To achieve new breakthroughs, the scale of our nation's response must match the scale of the problem," Dr. Blayney said. "The cancer community has a long road ahead before we reach President Obama's goal of finding 'a cure for cancer in our time'."

J Clin Oncol. Published online November 9, 2009. Abstract

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