榴莲视频

CHICAGO – Combination of the investigational agent cediranib and olaparib (Lynparza) was active against ovarian cancers that were both platinum-sensitive and platinum therapy resistant, researchers said here.

In her poster presentation, Joyce Liu, MD, of Dana-Farber Cancer Institute/Harvard Medical School in Boston, said that 74% of the 35 women in the study who had platinum-sensitive tumors had an objective response to the combination of the agents, including several patients whose response has continued for more than a year.

She also told 榴莲视频 at the annual meeting of the American Society of Clinical that about 20% of the 35 women in the study who had platinum-resistant tumors also responded to the combination therapy.

Liu said that one of the objectives of the current study was to determine if there were biomarkers that could be used to guide therapy. "We don't have a great sense of the mechanism of synergy," she said. "We confirmed the activity of the combination in platinum-sensitive patients. We see that BRCA status is a biomarker of response for this combination but we think there will be other biomarkers as well."

The average age of the women in the study was 60.9 years; 49% of the women had BRCA wild-type genetics; 27% of the women had BRCA mutations; the BRCA status was unknown in 17% of the women. About 40% of the women had tried one previous line of therapy; another 40% had gone through two lines of therapy and 20% had three or more previous therapies.

Women entered the trial if they had recurrent high-grade serous or high-grade endometroid primary peritoneal, Fallopian tube or ovarian cancer. Patients were ineligible if they had previously been treated with a PARP inhibitor or an anti-angiogenic agent.

"Further molecular studies are needed," Liu said, suggesting that further findings would be available at later meetings.

Therapeutic Vaccine for Cervical Cancer

Researchers reported encouraging initial results using a therapeutic vaccine for the treatment of advanced cervical cancer.

Of 10 patients treated with the combination of radiation and MEDI0457 for advanced or recurrent/persistent cervical cancer, eight remain alive with no evidence of disease after at least 36 months. One of those patients remains alive at 60 months; two others remained alive at 48 weeks, said Yasmin Hasan, MD, of the University of Chicago.

The vaccine targets the human papilloma virus HPV-16 and HPV-18 – also targets of human papilloma virus preventive vaccines which have been available for a decade.

More than half the patients treated with the vaccine candidate developed detectable immune responses to human papilloma virus HPV-16 and HPV-18, Hasan told 榴莲视频 at her poster presentation.

"Adjuvant MEDI0457 is feasible after chemoradiation for locally advance and/or recurrent cervical cancer," she said. "The results support further studies into adding MEDI0457 to the chemoradiation regimen for women with advanced or recurrent/persistent cervical cancer," she said.

Most of adverse events were injection site reactions, Hasan said. One person in the study died after an intestinal perforation, not believed to be caused by the vaccine.

"The way this works is that the vaccine goes inside the muscle cell and integrates with the person's DNA," she explained, and then the vaccine will stimulate the person's immune system to attack the cancer.

In the phase I/II study, the vaccine was delivered to patients at baseline and then at weeks 4, 8 and 12. The primary endpoint was safety and tolerability, with secondary endpoints being immune responses against human papilloma virus antigens. Four of the patients was diagnosed with squamous cell cervical cancer; six were diagnosed with adenocarcinoma. Seven of the patients were newly diagnosed; three were recurrent or had persistent disease.

No Survival Benefit With Bevacizumab

The final analysis of a government-supported clinical trial showed no overall survival difference between patients who were treated with chemotherapy plus bevacizumab (Avastin) compared with ovarian cancer patients treated with chemotherapy alone.

However, Krishnansu Tewari, MD, of the University of California Irvine, said at his poster presentation, "This result is not surprising because it is very difficult to show in these studies a survival benefit because this disease responds to so much chemotherapy. So once the patients comes off the trial, as investigators we can't control the type of chemotherapy given. That ultimately dilutes the overall survival."

In the trial the median overall survival for the patients who were not initiated on bevacizumab was 32.6 months while those who started on bevacizumab had median overall survival of 34.5 months (P=0.53), Tewari told 榴莲视频.

"What the study did show was a significant improvement in progression-free survival which was the primary endpoint of the study," he said. "The progression-free survival was a difference of about 4 months – 14.1 months for patients on bevacizumab and 10.2 months for patients not taking bevacizumab (P<0.001)." Those results released in 2010 had 17.2 months of follow-up. The current analysis has 102 months of follow-up.

"There is a chance that the results of this study will allow bevacizumab to receive approval for use in the first-line setting," Tewari said.

In the NRG Oncology/Gynecologic Oncology Group study, 1,873 women with newly diagnosed, incompletely resected Stage III or Stage IV ovarian cancer were recruited. Currently 204 women remain alive but have experienced a progression event; 178 women are alive without any progression.

The patients were assigned to three study arms: placebo plus carboplatin and paclitaxel with 625 women; bevacizumab, carboplatin and paclitaxel, with bevacizumab replaced by placebo after six cycles of treatment with 625 women enrolled; bevacizumab plus carboplatin and paclitaxel with bevacizumab maintenance therapy being continued throughout the trial after six cycles of chemotherapy with 623 women assigned to this arm.