The significant live-saving potential of a simple vinegar test used in India to cut cervical cancer deaths by one-third was revealed at the ASCO 2013 annual meeting in Chicago.
The ASCO 2013 plenary session on Sunday, June 2 heard that biennial screening for cervical cancer by trained non-medical personnel using acetic acid reduced cervical cancer mortality by 31%. This 15-year randomised, controlled trial was conducted among 150,000 women in the slums of Mumbai.
The presenter, Dr Surendra Shastri, professor of preventive oncology at the Tata Memorial Hospital in India, said that cervical cancer is the most common and most deadly cancer among Indian women due to the scarcity of basic health resources and access to preventive medicine.
Nearly 142,000 cases of cervical cancer occur each year in India alone, and annually more than 77,000 Indian women die of the disease. When viewed from a global perspective, these figures account for approximately 30% of the burden of cervical cancer worldwide, he added.
In 1992 and again in 2006, the Indian government determined that inadequate infrastructure, lack of trained personnel, logistic difficulties, and the relatively high cost of large-scale Pap screening posed too great a drain on restricted resources.
Dr Shastri and colleagues proposed that VIA – visual inspection with acetic acid – was a rapid and inexpensive test that offers a practical alternative to Pap smears or HPV DNA testing in resource-limited settings.
He explained that 60 seconds after applying acetic acid to the cervix using a cotton swab, precancerous lesions turn white and can be discerned from pink healthy tissue with the naked eye – something that primary health workers can easily be trained to identify with high accuracy.
In order to evaluate the feasibility of using VIA as a large-scale cervical cancer screening programme, Dr Shastri and colleagues initiated a study in 1998, enrolling more than 151,000 women age 35-64 who had no prior cancer history. Half of the women were randomly assigned to receive four rounds of cancer education and VIA every two years. The other half received no screening – ‘the current standard of care in India’ – and one-time cancer education at recruitment.
All women in the screening group who tested positive by VIA, and those in the control group who noticed signs or symptoms of cervical cancer taught to them at enrolment, were directed to Tata Memorial Hospital or other facilities for diagnosis. Those with confirmed disease received free cervical cancer treatment.
“There was a certain amount of over diagnosis at the beginning, which was very small, which is universal in all screening trials. However, at around eight years, over-diagnosis ceases, so one of the important things in the study is there is almost zero over-diagnosis. This is a crucial factor in low-resource settings where the public health systems are already overburdened,” said Dr Shastri.
He reported that VIA enabled diagnosis at an earlier stage of the disease and hence earlier treatment, which translated into survival gains. Use of VIA significantly reduced the rate of cervical cancer mortality from 16.22 to 11.12 deaths per 100,000 women-years of observation – that’s a 31% reduction compared with the control group.
Dr Shastri estimated that, if implemented in developing countries that have little or no access to Pap screening, this easy-to-use procedure could ultimately prevent 22,000 deaths from cervical cancer in India and 72,000 deaths in low-resource countries worldwide each year.
Bevacizumab - new hope for cervical cancer
Details of the first molecularly-targeted agent to improve overall survival in a gynaecologic cancer were also presented during the Sunday plenary session. Angiogenesis inhibitor bevacizumab was found to significantly improve overall survival (OS) when added to chemotherapy for patients with recurrent/persistent or metastatic cervical cancer, according to results of a planned interim analysis of the Gynecologic Oncology Group (GOG) 240 study.
“Unfortunately, women with metastatic and recurrent cervical cancer have very few therapeutic options. The standard regimen of cisplatin plus paclitaxel is associated with median OS of under 12 months,” said Dr Krishnansu Sujata Tewari, professor of obstetrics and gynaecology at the University of California (UC) Irvine Medical Center.
The GOG 240 study assigned patients to either of two chemotherapy regimens involving cisplatin plus paclitaxel or topotecan and paclitaxel, and then randomly assigned patients to receive 15mg/kg of bevacizumab or not. Treatment cycles were repeated every 21 days until disease progression, unacceptable toxicity, or complete response. More than 70% of patients in both groups had received prior platinum-based therapy, he explained.
“In conclusion, the study met its primary end-point with the regimens administering bevacizumab resulting in improved median overall survival. The 3.7-month improvement is felt to be clinically meaningful and is consistent with the goal we had set out when designing this study.
“The effect of bevacizumab was sustained with multiple prognostic factors including when the disease was in the previously irradiated pelvis. Importantly, the control arm did not underperform. The 13.3 months noted with chemotherapy alone for overall survival is similar to that reported for cisplatin plus paclitaxel in our previous study GOG204.
“In addition, the bevacizumab regimen improved progression-free survival (PFS) and objective tumour response rates. We saw no new adverse events in this population of patients, which includes patients that had been heavily pre-irradiated, and although both thromboembolic events and fistula were increased in the bevacizumab-containing arms, these rates were relatively low and below 10%. Most importantly the improvement in overall survival associated with bevacizumab treatment was not accompanied by a significant decrease in health-related quality of life,” he stressed.
Discussant for the session Dr Gottfried Konecny, of the David Geffen School of Medicine at UC, Los Angeles, remarked that there is “an extraordinarily good rationale” for targeting VEGF in this disease setting.
“I think GOG 240 can be seen as a practice-changing study,” he added. “I think for cervical cancer it is incredibly important to move bevacizumab into earlier disease stages…. Maybe this is a situation where the benefit of [the drug] will translate into a reduction in mortality.”
Glioblastoma: More research needed
A separate presentation of results of a large multicentre trial showed no benefit from bevacizumab in patients with newly diagnosed glioblastoma. Patients lived about 16 months whether they received chemoradiation alone or with the angiogenesis inhibitor.
The addition of bevacizumab to chemoradiation did add to toxicity. However, progression-free survival (PFS) increased with bevacizumab, but the difference did not reach the pre-specified target in the Radiation Therapy Oncology Group (RTOG) 0825 phase III trial, according to Dr Mark Gilbert, of The University of Texas MD Anderson Cancer Center, who presented the results.
“It is also possible that bevacizumab will prove to improve overall survival but we need to identify the specific subgroup of patients.
“We now know, thanks to the TCGA and Rembrandt molecular and genetic databases, that there are at least five major different types glioblastoma molecular subtypes, and probably more, so it will be a challenge to see which of these subtypes, if any, show improved benefit with bevacizumab,” said Dr Gilbert.
Dr Surendra Shastri, professor of preventive oncology, Tata Memorial Hospital, India. Photo by © ASCO/Silas Crews 2013
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