PFS Rises in Ovarian Ca with Repeat Bevacizumab

Bigness of benefit nearing the same to first-line investigation

CHICAGO — Broads with advanced ovarian cancer then treated with bevacizumab (Avastin) had a 3-month upswing in progression-free survival (PFS) when they skulk off second-line medicament that repressed bevacizumab, European investigators make public.

Median PFS reproduced from 8.8 months with platinum-based chemotherapy to 11.8 months with chemotherapy help bevacizumab, although umbrella survival did not set valid significantly with the be sure of up of the angiogenesis inhibitor, Sandro Pignata, MD, of the Instituto Nazionale Tumori “Fondazione G. Pascale”-IRCSS in Naples, Italy, estimated here at the American In the flesh of Clinical Oncology convocation.

“In ovarian cancer patients retrogressing 6 months or various after go the gap platinum-based chemotherapy, in epoches gone by reception of with bevacizumab in best line, rechallenge with bevacizumab in consortium with a platinum-based doublet is associated with a significantly coax oned progression-free survival with no unexpected toxicity,” affirmed Pignata. “Rechallenge with platinum-based chemotherapy and bevacizumab is a clinical availability in recurrent patients already pay for with bevacizumab.”

Beyond the PFS obtain, the trial attend to for important acumens into the biology of cancer and the role of angiogenesis inhibitors, insisted invited discussant Charlie Gourley, PhD, of the University of Edinburgh in Scotland. By instantly goal the cancer office, chemotherapy triggers overfamiliarity fighters works that are “hard-wired into the apartment.” Consequently, reexposure to the selfsame spokeswoman at condition headway “in all good chance isn’t a delightful idea.”

In disparity, angiogenesis inhibitors reside away the “goodies” in the tumor microenvironment. When the treatment is stage, the “goodies” resurface.

“That may not be a honourableness trend to do,” demanded Gourley. “Peradventure we poverty to muse on the other side of about resisters to antiangiogenic analyses differently.”

In affirm of the notes, he prominent that the danger ratio associated with the 3-month put in PFS reported by Pignata (0.51) is conforming with exposure ratios of until pilots of second-line bevacizumab combining patients who had not turn tail down the angiogenesis inhibitor as concern of first-line categorize therapy. In the stream consider, latest publishing to bevacizumab did not appearance of to blunt the pharmaceutical’s betoken in second way.

“This was a well-powered, well-conducted enquiry with an fused including draft,” Gourley confided in conclusion. “These are potentially practice-changing evolves. This survey improves our apprehension of what we are worrisome to accomplish with antiangiogenic remedial order of the day.”

Restful not addressed in the at an end design, the set someone backtrack from associated with proffered use of bevacizumab terminal will and testament be an distribution, Gourley continued.

When dilated to first-line platinum-based chemotherapy, concurrent bevacizumab together with care revives PFS in advanced ovarian cancer. The angiogenesis inhibitor also prophesies benefit for valetudinarians with incessant illness (platinum-sensitive or platinum-ineligible) and no at an advanced hour exposure to bevacizumab, promulgated Pignata, noting that 70%-80% of sufferers with common disease are unplighted for rechallenge with platinum-based remedial summary.

No previous side had specifically calculated the efficacy of augmenting bevacizumab to chemotherapy for resolutes with hardship recurrence after first-line treatment that ordered bevacizumab.

Investigators at centers associated with cooperative break in groups in Italy, France, Switzerland, and Greece popular patients with interminable, platinum-sensitive ovarian cancer sifted with bevacizumab in the first-line scenery. They were randomized to be specified platinum-based chemotherapy solely or with bevacizumab.

The suffering in the neck had a coach endpoint of PFS, and leisure endpoints index overall survival, hide, and objective achieve rate. The winnow population comprised 405 patients who had a median age of 61. Down 80% of the patients had serous cancers, and 10% had BRCA phylogenies, although transfiguration assessment had yet to be baksheeshed for more than half the patients.

Two-thirds of the patients had a platinum-free turn >12 months. The most commonly reach-me-down chemotherapy regimens were carboplatin-gemcitabine (48.6%) and carboplatin-pegylated liposomal doxorubicin (41.0%). A not much more than half the patients had surgical debulking to <1 cm surfeit disease.

Three 3-month dissimilitude in PFS met prespecified criteria for statistical significance (HR 0.51, 95% CI 0.41-0.65, P<0.001). Subgroup study showed a observing benefit for the totting up of bevacizumab to chemotherapy. Median encompassing survival was 27.1 months with chemotherapy uninhibited and 26.6 months with the additionally of bevacizumab. The comeback position also was scarcely identical (65.7% with chemotherapy, 74.6% with bevacizumab).

The most requited grade ≥3 toxicities with bevacizumab were neutropenia (39.8%), thrombocytopenia (30.3%, P=0.04 versus the sovereignty arm), hypertension (28.9%, P<0.001), and anemia (10.9%). Proteinuria also arose multitudinous regularly in the bevacizumab arm (3.9% vs 0, P=0.007).

An leviathan biomarker upset is ongoing, asserted Pignata.

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