New Data Shows Cancer Treatment Avastin® Can Extend Lives Of Women With Advanced Cervical Cancer

Dr. Enrique Jacome

New data showing cancer treatment Avastin® (bevacizumab) can extend the lives of women with advanced cervical cancer compared to chemotherapy alone has been published in the New England Journal of Medicine. In the last decade the incidence of cervical cancer has risen by approximately 15% in the UK with 2,900 women diagnosed in 2010.² Until now there have been limited clinical advances with patients only having a choice of traditional chemotherapies.

The data from a study known as GOG240 show that the addition of targeted therapy Avastin to chemotherapy (paclitaxel and topotecan or cisplatin) significantly extends the lives of women with advanced cervical cancer (stage IVB, recurrent or persistent cervical carcinoma) by nearly four months and almost 30% compared to chemotherapy alone (median overall survival of 17 months compared to 13.3 months, respectively; HR=0.71, p=0.0035).³

In addition, the percentage of patients who responded to therapy increased by a third from 36% to 48% (p= 0.0078) with the addition of Avastin compared to chemotherapy alone.³Patients receiving Avastin experienced more side effects than those who did not, but they were consistent with those previously associated with Avastin and did not impair patients' quality of life.^1,4 Avastin is not currently licenced for the treatment of advanced cervical cancer.4

Dr Mary McCormack, Consultant Clinical Oncologist at University College London Hospitals NHS Foundation Trust said: "There is a desperate need for more treatment options for advanced cervical cancer, so it is very encouraging to see that Avastin given with chemotherapy extends survival by four months without compromising patients' quality of life."

Robert Music, Chief Executive of Jo's Cervical Cancer Trust, said: "For women who receive a late stage diagnosis of cervical cancer the prognosis can often be poor. Any advances that can help improve outcomes and overall survival rates in women with advanced cervical cancer are welcome."

GOG240 is an independent phase III trial sponsored by the US National Cancer Institute (NCI) and is the first study to show a targeted therapy significantly improves overall survival in gynaecological cancer.³ It was conducted by a network of researchers led by the US Gynecologic Oncology Group (GOG).³

Roche remains committed to improving outcomes for cancer sufferers and while GOG240 is not a Roche study we are working with regulatory authorities to seek a licence for Avastin in advanced cervical cancer.

Cervical cancer by numbers:²

• Around 2,900 women in the UK were diagnosed with cervical cancer in 2010.
• Approximately 1,000 women died from the disease in 2011.
• Cervical cancer is the most common cancer in UK women aged 35 and under.

The New England Journal of Medicine also published data from two studies known as AVAglio and RTOG 0825 on the treatment of newly diagnosed aggressive brain cancer glioblastoma (GBM) with Avastin.^5,6 There are limited treatment options for newly diagnosed GBM and prognosis is extremely poor.⁷ As previously reported, the AVAglio study investigators observed a statistically significant improvement in progression free survival (PFS),⁸which is important for patients as it preserves neurological function and effectively extending the time between first diagnosis and progression is a key goal for oncologists. The latest results of the AVAglio study show a trend towards improved overall survival when Avastin is added to standard treatment (11% reduction in risk of dying) but this was not significant.⁵The results of the RTOG 0825 study showed an improvement in PFS from 7.3 to 10.7 months (HR=0.79, p=0.007), however this improvement did not reach the level of significance pre-specified in the study.⁹ Avastin is not licenced for newly diagnosed GBM.⁴

Avastin has a well-established tolerability profile in the treatment of cancer; the most frequently observed adverse drug reactions in clinical trials of Avastin were hypertension, fatigue or asthenia, diarrhoea and abdominal pain.⁴The most common side effects are generally manageable, for example, hypertension can usually be managed with conventional antihypertensive treatment.⁴

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HIV Drug Used To Reverse Effects Of Virus That Causes Cervical Cancer

Dr. Enrique Jacome

A commonly-used HIV drug has been shown to kill-off the human papilloma virus (HPV) that leads to cervical cancer in a world-first clinical trial led by The University of Manchester with Kenyatta National Hospital (KNH) in Nairobi.

Drs Ian and Lynne Hampson, from the University's Institute of Cancer Sciences and Dr Innocent Orora Maranga, Consultant in Obstetrics and Gynaecology at KNH in Nairobi examined Kenyan women diagnosed with HPV positive early stage cervical cancer who were treated with the antiviral HIV drug lopinavir in Kenya.

The study looked at 40 women with both high and low-grade pre-cancerous disease of the cervix and the antiviral drug, normally used orally to treat HIV, was self-applied directly to the cervix as a pessary.

The results, due to be presented at two international scientific conferences later this month and next, showed a high proportion of women diagnosed with HPV positive high-grade disease returned to normal following a short course of the new treatment.

The findings build on previous peer-reviewed laboratory based research carried out by Drs Hampson and will be submitted to a journal soon. They have been described by an independent leading specialist in gynaecological cancer as very impressive.

The 40 women, who were all HPV positive with either high-grade, borderline or low grade disease, were treated with one capsule of the antiviral drug twice a day for 2 weeks. Repeat cervical smears showed a marked improvement within one month of the treatment although after three months, there was a definite response. Out of 23 women initially diagnosed with high-grade disease, 19 (82.6%) had returned to normal and two now had low-grade disease giving an overall positive response in 91.2%.of those treated. Furthermore the 17 women initially diagnosed with borderline or low-grade disease also showed similar improvement.

Photographic images of the cervix before and after treatment showed clear regression of the cervical lesions and no adverse reactions were reported.

Dr Ian Hampson said: "For an early stage clinical trial the results have exceeded our expectations. We have seen women with high-grade disease revert to a normal healthy cervix within a comparatively short period of time.

"We are convinced that further optimisation of the dose and treatment period will improve the efficacy still further.

"It is our hope that this treatment has the potential to revolutionise the management of this disease most particularly in developing nations such as Kenya."

Cervical cancer is caused by infection with human papilloma virus (HPV) and is more than five times more prevalent in East Africa than the UK. In many developing countries, HPV-related cervical cancer is still one of the most common women's cancers accounting for approximately 290,000 deaths per year worldwide. The same virus also causes a significant proportion of cancers of the mouth and throat in both men and women and this disease is showing an large increase in developed countries, such as the UK, where it is now more than twice as common as cervical cancer.

Dr Lynne Hampson said: "Current HPV Vaccines are prophylactics aimed at preventing the disease rather than curing or treating symptoms. Other than surgery, as yet there is no effective treatment for either HPV infection or the pre-cancerous lesion it causes which is why these results are so exciting.

"Further work is needed but it looks as though this might be a potential treatment to stop early stage cervical cancer caused by HPV."

On a global scale HPV is the most common sexually transmitted disease. Although in the developed world vaccination programmes against HPV are well underway, these are not effective in women already infected with the virus. The current vaccines do not protect against all types of HPV and they are expensive, which can limit their use in countries with low resources.

The researchers believe their findings offer a potential cheap and preferably self-administered treatment that could eliminate early-stage HPV infections before these have developed into cancers would therefore have distinct health advantages. Approximately 300,000 women are dying from cervical cancer per annum which is equivalent to 800 per day, one every two minutes mostly in low resource settings.

The research has been backed by Lord Saatchi, whose wife novelist Josephine Hart died of ovarian cancer and has submitted a Private Member's Medical Innovation Bill to Parliament which he argues would promote "responsible" innovation for medics to try new treatments without the fear of negligence claims. The bill comes amid claims there is currently an estimated average time lag of 17 years for a new treatment or research evidence to reach clinical practice in the UK.

Lord Saatchi said: "What Drs Lynne and Ian Hampson have done is amazing - a classic case of innovation. The fact that they needed to run their trial in Nairobi and that even now there is no guarantee the treatment will be available in the UK any time soon, is a source of immense frustration."

Dr Ian Hampson added: "This is not something we could have done in the UK due to the associated costs and red tape. We have full ethical approval in Kenya and chose to conduct the trial there because of the extreme need for a self-applied treatment for early stage cervical cancer. "During the trial we provided 820 women with free cervical smear testing in addition to a range of other free medical tests that are not routinely available in Kenya. This was essential in order to identify women with HPV related cervical disease so that we could treat them with lopinavir. It is very significant that during this process we also identified five women who already had invasive cervical cancer and these were immediately referred for surgery."

The research was funded by the UK Philanthropist Mr Ken Chorlton, the Caring Cancer Trust, United in Cancer Charitable Trust, The Humane Research Trust, Quest Cancer, the Cancer Prevention Research Trust and Hologic.

Professor Pierre Martin-Hirsh, Consultant in Gynaecological and Oncologist and Associate Editor in Chief, the British Journal of Obstetrics and Gynaecological, has described the research as very impressive.

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Research Shows An Increased Blood Clot Risk In Women For At Least 12 Weeks After Birth

Dr. Enrique Jacome

According to the Centers for Disease Control and Prevention, women have an increased risk of blood clots for up to 6 weeks after giving birth. But new research suggests that the risk of a blood clot remains higher than normal for a minimum of 12 weeks after delivering a baby.

The research team, led by Dr. Hooman Kamel of the Department of Neurology and the Brain and Mind Research Institute of Weill Cornell Medical College in New York, presented the study findings at the American Stroke Association's International Stroke Conference 2014.

Blood clotting, also known as coagulation, is a process that stops excessive bleeding when a blood vessel is injured. Blood cells called platelets work with proteins in the plasma of the blood to form a clot over the area of injury.

The body usually dissolves the blood clot once the injury has healed. But at times, clots can form inside the blood vessels without naturally dissolving. In this case, blood can build up behind the clots, causing swelling and pain. The clots can also block the return of blood to the heart, which can cause heart attack and stroke.

The American Society of Hematology state that women are at a higher risk of blood clots during and shortly after pregnancy. Pregnant women tend to form blood clots in the deep veins of the legs or the pelvic area, which is known as deep-vein thrombosis (DVT).

Blood clots can also lead to pulmonary embolism (PE) - a condition in which a blood clot detaches and blocks the main artery of the lungs.

Postpartum blood clot risk increased for 12 weeks after birth

For the study, the investigators analyzed data of 1,687,930 women who gave birth at a hospital in California between 2005 and 2010.

Of these women, 1,015 suffered blood clots during the 1.5 years after giving birth. Some of the women experienced stroke, heart attack, PE or DVT as a result of the clots.

Using the data, the researchers found that during weeks 0-6 after birth, the risk of a blood clot for the women was 10.8 times higher. Blood clot risk was 2.2 times higher during weeks 7-12, and 1.4 times higher during weeks 13-18.

The investigators note that the increased risk during weeks 13-18 was "non-significant" and the risk of a blood clot returned to normal by weeks 19-24.

The research team says that although fewer than 1 in 10,000 women suffer a blood clot related to pregnancy in the 6 to 12 weeks after birth, the seriousness of blood clots in this population should not be overlooked.

Dr. Kamel says:

"While rare, blood clots are a serious cause of disability and death in pregnant and postpartum women, and many members of our research team have cared for young women with these complications.

Clinicians should consider our results when caring for high-risk postpartum patients, such as those with previous clots, or postpartum patients with symptoms concerning for thrombosis."

The investigators add that women who have recently given birth should seek medical attention if they experience chest pressure or pain, swelling or pain in one leg, have difficulty breathing, develop a sudden severe headache, or have sudden loss of vision, speech, balance or strength on one side of the body.

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Research Shows Young Female Smokers At Higher Risk Of Common Breast Cancer Type

Dr. Enrique Jacome

New research suggests that young women who currently smoke and who have smoked one pack of cigarettes a day for 10 years or more have a much higher risk for estrogen receptor-positive breast cancer - the most common form of the disease - compared with women who have smoked for a shorter period of time. This is according to a study recently published in the journal Cancer.

The research team, led by Dr. Christopher Li of the Fred Hutchinson Cancer Research Center in Seattle, WA, says there is quite a bit of research that has associated smoking among young women with an increased risk of breast cancer. But they say few studies have assessed the link between smoking and subtypes of breast cancer.

For their study, the investigators analyzed 778 women who had estrogen receptor-positive breast cancer, 182 women with triple-negative breast cancer, and 938 women who were cancer-free.

When the breast cancer cells have a significant number of receptors for estrogen, this is classed as estrogen receptor-positive breast cancer. This type of cancer is more likely to respond to hormonal therapies.

Triple-negative breast cancer means the breast cancer cells are not positive to receptors for estrogen, progesterone or HER2. This form of breast cancer is usually more aggressive.

All patients were aged between 20 and 44 years, and those with breast cancer were diagnosed with the disease between 2004 and 2010.

The researchers asked the women about their smoking history. This included information on whether they have ever smoked, whether they still smoke, how much they have smoked in the past/currently smoke, and for how long they have smoked.

Risk increases by 60% with 10-year smoking history

The results of the study revealed that women who had ever smoked (more than 100 cigarettes in their lifetime) had a 30% increased risk of breast cancer overall, compared with never smokers (fewer than 100 cigarettes in their lifetime).

However, the researchers found that young women who were current or recent smokers, and who had been smoking one pack of cigarettes a day for at least a decade, were 60% more likely to develop estrogen receptor-positive breast cancer, compared with women who had smoked for fewer years and those who had a history of fewer pack-years. The researchers found no link between smoking in young women and the risk of triple-negative breast cancer.

Commenting on the findings, the researchers say:

"The current study adds to recent evidence indicating that smoking is modestly associated with breast cancer risk in young women.

Expanding on earlier work, our findings suggest that this association is limited to an increase in the risk of estrogen receptor-positive breast cancer and that smoking does not have an impact on the risk of triple-negative breast cancer."

The researchers conclude that since there is consistently strong evidence that smoking in young women may increase the risk of breast cancer, there should be ongoing efforts to prevent young women from taking up smoking and increased awareness surrounding the risks of smoking in this population.

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Research Shows Postnatal Appointments After Childbirth Is A Window Of Opportunity For Preventive Care

Dr. Enrique Jacome

Medical associations widely recommend that women visit their obstetricians and primary care doctors shortly after giving birth, but slightly fewer than half make or keep those postpartum appointments, according to a study by Johns Hopkins researchers.

The researchers found that women with pregnancy complications were more likely to see a doctor post-delivery, but overall, visit rates were low.

"Women need to understand the importance of a six-week visit to the obstetrician - not only to address concerns and healing after delivery, but also to follow up on possible future health risks, review the pregnancy and make the transition to primary care," says Wendy Bennett, M.D., assistant professor of medicine and the lead researcher for the study, described online last week in the Journal of General Internal Medicine. "Women with pregnancy complications are at higher risk for some chronic diseases, such as diabetes, high blood pressure and heart disease, and these visits are an opportunity to assess risks and refer to primary care providers to work on long-term preventive care."

Physician groups, such as the American College of Obstetrics and Gynecology, recommend women with complications like high blood pressure during pregnancy or gestational diabetes not only visit their obstetricians six weeks after a birth, but that they also see their primary care doctors within a year.

For the study, the researchers collected data from one commercial health insurance plan and multiple Medicaid insurance plans in Maryland. The aims were to determine different predictors of receiving post-delivery primary and obstetric care in women with and without pregnancy complications, including gestational or pregestational diabetes mellitus and hypertensive disorders, such as preeclampsia. Women with these conditions are much more likely to develop long-term health problems, such as type 2 diabetes and cardiovascular disease.

Among women with tax-supported Medicaid insurance, 56.6 percent of those with a complicated pregnancy and 51.7 percent of those without a complicated pregnancy visited a primary care doctor within a year. Among women with commercial health insurance, 60 percent of those with a complicated pregnancy and 49.6 percent of those without a complicated pregnancy did so.

White patients, older patients and patients with depression or preeclampsia were also more likely to visit their primary care doctor.

Of the women on Medicaid, 65 percent of those with complicated pregnancies and 61.5 percent of those without complicated pregnancies had a postpartum obstetric visit within three months. Numbers were slightly lower for those with commercial insurance, at 50.8 percent of those with complicated pregnancies and 44.6 percent of those without complicated pregnancies.

Bennett says providers need to develop creative ways to improve attendance at postpartum visits. A pilot project at Johns Hopkins Bayview Medical Center, for example, involves combined "mommy-baby" visits, she says. If the baby's checkup is included in the mother's visit, the mother may be more likely to keep the appointment, and thus would receive important education about improving health behaviors and the need for primary care follow-up. Other options are home visits and collaborations with day care centers, community centers and churches to make visits and health promotional activities more convenient.

Bennett says more work is also needed by hospitals and physicians to coordinate future appointments, or to arrange transportation or child care if needed.

"Pregnancy is a teachable moment - many women are very motivated to make healthier lifestyle choices to keep themselves and their babies healthy. After a birth, we need to keep them motivated," she says.

Bennett and her team say their findings add to evidence that access to health care alone - having insurance and a physician - is not enough to assure proper care. All study participants had insurance for at least six weeks after delivery.

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