Two study groups reported in the December 29, 2011, issue of the New England Journal of Medicine the findings of their Phase III investigations of use of the targeted therapy Avastin (bevacizumab) in advanced ovarian cancer (CaO).

The ICON7 Investigators assessed the use of Avastin in a trial involving 1,528 women, 70% of whom had Stage IIIc or Stage IV CaO. One group received standard therapy of carboplatin and paclitaxel and the other received the standard therapy plus Avastin. At 36 months, progression-free survival in the standard therapy arm was 20.3 months; in the standard+Avastin group, it was 21.8 months. At 42 months, progression-free survival was 22.4 and 24.1 months, respectively. Patients at high risk of progression achieved a greater benefit with Avastin; progression-free survival among these patients at 42 months was 14.5 months in the standard therapy group and 18.1 months in the standard+Avastin group. For these high-risk patients, overall survival was 28.8 months and 36.6 months, respectively.

The Gynecologic Oncology Group (GOG) enrolled 1,873 women with newly diagnosed Stage III or IV CaO and randomized them into three arms. One group received standard therapy of paclitaxel and carboplatin; another, the Avastin-initiation group, received standard therapy plus Avastin in cycles 2-6; the third, the Avastin-throughout group, received standard therapy plus Avastin in cycles 2-22. Progression-free survival at 10.3 months was assessed. In the standard therapy group, it was 10.3 months; in the Avastin-initiation group, it was 11.2 months; and in the Avastin-throughout group, it was 14.1 months.

The GOG group's lead investigator, Robert A. Burger, M.D., said of the findings: "This approach can be looked upon as a third major component of treatment for ovarian cancer and related malignancies. This represents a new way for us to control the disease."

Previously, the ongoing First-Line Erbitux in Lung Cancer (FLEX) study showed that adding cetuximab (Erbitux) to chemotherapy benefited patients with advanced non-small-cell lung cancer (NSCLC). Which patients are most likely to benefit, though?

The latest findings from FLEX, published in The Lancet Oncology, show that epidermal growth factor receptor (EGFR) expression plays a role. To assess that role, researchers used prospective EGFR tumor expression data to place subjects into two groups, those with high EGFR expression and those with low EGFR expression.

Patients with high EGFR expression experienced longer survival when cetuximab was added to the treatment regimen: in this group, overall survival (the study's primary end point) was extended to a median of 12 months, versus 9.6 months for the chemotherapy-only group. For patients with low EGFR, overall survival was not improved by adding cetuximab: low-EGFR patients who received cetuximab in addition to chemotherapy survived for a median of 9.8 months, versus 10.3 months in the chemotherapy-only group.

The researchers conclude that EGFR expression can be used to guide treatment by indicating the likely benefit of cetuximab for certain patients.

A study recently published in the Journal of the American Medical Association looked at how BRCA1 and BRCA2 mutations and promoter hypermethylation relate to survival outcomes and chemotherapy response in ovarian cancer (CaO). This observational study relied on data from the Cancer Genome Atlas Project and looked at 316 CaO cases, 37 of which carried a BRCA1 mutation and 29 of which carried a BRCA2 mutation. As reported in MedPage Today, the small size of the study must be taken into account.

However, in the study, differences related to the mutation types were noted:

• Five-year overall survival was 61% for BRCA2 mutation cases, 44% for BRCA1 mutations, and 25% for wild-type BRCA mutation cases.



• Five-year progression-free survival rates were 39% for BRCA2 mutation cases, 13% for BRCA1 mutation cases, and 10% for wild-type BRCA mutation cases.



• Median responses to treatment with platinum-based chemotherapy were 18 months for BRCA2 mutation cases, 12.5 months for BRCA1 mutation cases, and 11.7 months for wild-type BRCA mutation cases.

An editorial accompanies the journal article; its authors point to the implications for new CaO therapies, including PARP inhibitors, that might be targeted to patients based on BRCA status.

A September article in Oncology points to the value of changing the treatment paradigm for bladder cancer. "Bladder Cancer: Imperatives for Personalized Medicine" points to the fact that this form of cancer is likely to grow in incidence worldwide. Early-stage treatment approaches vary widely; the cancer is the most expensive to treat based on Medicare data; and among patients receiving intensive treatment, overall survival rates are not improving, say the authors.

The authors advocate taking a new approach to the disease--finding standard ways to determine which forms of bladder cancer have lower risk of mortality and morbidity (generally, those that display mutations in fibroblast growth factor receptor 3 [FGFR3], for instance) and which forms are more lethal (generally, those with abnormalities in p53 and Rb). In this way, appropriately less intensive treatment can be directed to lower risk patients and trials can focus on relevant patient groups. These are just two aspects of the paradigm shift that is needed, however.

For instance, the authors write, "Unfortunately, we currently have inadequate insight into the genetic or epigenetic changes that may direct transformation of low-grade noninvasive tumors into high-grade invasive ones. Identification and clinical validation of markers that reliably distinguish divergent pathways of behavior are required to advance real-world personalization of surgical and medical management of these tumors."

The authors call for intensified research and greater experimentation in finding potential targets so that novel treatments can be developed, given "the imperative to improve outcomes for individual patients."

A Phase I trial recently published in Nature showed that a genetically modified poxvirus, JX-594, can be intravenously administered to selectively target cancer therapies, replicate, and retard growth of cancerous tissue. Noncancerous tissue was not affected. The treatment was generally well tolerated.

Patients in the trial had treatment-refractory solid-tumor cancers of various types. They received one intravenous injection. JX-594 targeted cancers that express the epidermal growth factor receptor (EGFR).

Said the study authors in Nature: "This platform technology opens up the possibility of multifunctional products that selectively express high concentrations of several complementary therapeutic and imaging molecules in metastatic solid tumours in humans." One study author was further quoted in Medpage Today: "The study is also important because it shows that we can use this approach to selectively express foreign genes in tumors, opening the door to a whole new suite of targeted cancer therapies."

Kris Carr's 2003 diagnosis with a rare from of cancer--hemangioendothelioma--was life-changing indeed. As she told the New York Times in a recent interview, "I realized that if I was going to make it through this, I needed to become the C.E.O. of my own healing start-up."

What followed was a documentary, several published books, and Web sites including crazysexycancer.com--in fact, N-of-One founder and president Jennifer Carter contributed to that site in July of 2010; you can read her post here.

Now, Carr heads up a company called Crazy Sexy Wellness and is transforming her various sites into a new site called crazysexylife.com. All of this is part of her move to address wellness overall--to explain how to be what she calls a "cancer thriver" rather than a cancer survivor. The move reflects what Ellen Stovall of the National Coalition for Cancer Survivorship calls a "new era." Said Stovall to the New York Times: "With cancer, it's not 'death or cure' anymore. You see the word 'chronic' a lot more. It's a very different way to live with it--and many need to figure out how."

Research recently published in the British Journal of Cancer found that overexpression of epidermal growth factor receptor (EGFR) was correlated with cervical squamous cell carcinomas.

The amplification was detected in 10.2% of samples and shown to be correlated with shorter overall survival. However, treatment with AG-1478 produced results in EGFR-overexpressing cells, inactivating EGFR and stalling tumor development and progression in a mouse model.

The researchers conclude that "anti-EGFR therapy may benefit patients who carry the 7p11.2 amplicon in their tumours."

No similar pattern was seen with adeno/adenosquamous cell carcinomas of the cervix.

AG-1478 has also been investigated as a potential treatment for endometrial and ovarian cancers.