Don’t delay platinum-based chemotherapy in favor of single-agent non-platinum-based chemotherapy in patients with partially platinum-sensitive ovarian cancer, Italian researchers advised.
Introducing non-platinum chemotherapy to prolong the platinum-free interval (PFI) in patients with progressing ovarian cancer who experience disease recurrence, or disease progression 6 to 12 months, after the last platinum-based chemotherapy (PBC) did not lead to a survival advantage, according to Sandro Pignata, MD, of the Istituto Nazionale per lo Studio e la Cura dei Tumori in Naples, and colleagues.
Overall survival (OS) and progression-free survival (PFS) were worse when platinum re-challenge was delayed for a median of 7.8 months after two planned treatments (experimental arm) compared with a delay of 0.01 months (standard arm), they wrote in the Journal of Clinical Oncology.
Median OS in the experimental arm was 21.8 months versus 24.5 months in the standard arm (hazard ratio 1.38, P=0.06). Median PFS was significantly shorter in the experimental arm versus the standard arm (12.8 months versus 16.4 months, HR 1.41 P=0.025). Global quality-of-life (QoL) change after three cycles was worse in the experimental arm but only slight differences were observed in the incidence of adverse effects.
“MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC [non platinum-based chemotherapy] in patients with partially platinum-sensitive [ovarian cancer],” the authors wrote, adding that “PBC should be used as a control arm in future trials of new drugs in this setting.”
These negative results may be the consequence of weak science behind the long-standing hypothesis that prolonging PFI with single-agent NPBC may offer a strategy to improve overall outcome, they suggested. In clinical practice, use of a NPBC is often favoured over platinum re-challenge, they pointed out.
“Therefore the time from last platinum treatment to recurrence (PFI) drives a treatment strategy that is based on non-platinum chemotherapy if PFI is less than 6 months (platinum resistant), and on platinum-containing doublets if PFI is more than 12 months (platinum sensitive),” the authors wrote. “There is uncertainty when the PFI is between 6 and 12 months (partially platinum sensitive) because of unsatisfactory results from treatment with platinum-containing doublets.”
The international, prospective, randomized, open-label, phase III MITO-8 trial enrolled 215 women with ovarian cancer from Feb. 26, 2009 to Oct. 16, 2015. They had experienced disease recurrence or disease progression 6 to 12 months after the last PBC, had received no more than two previous chemotherapy lines, and had a life expectancy of more than 3 months. Participants were randomly assigned 1:1 to either the standard or experimental arm.
The 108 women in the standard arm received PBC — combined carboplatin (Paraplatin) and paclitaxel (Taxol) — at current relapse followed by NPBC at subsequent relapse. In the experimental arm, 107 women received NPBC at current relapse followed by PBC at subsequent relapse.
NPBC initially consisted of pegylated liposomal doxorubicin (Doxil), but following an international shortage in August 2011, enrollment was interrupted. It resumed in April 2012 with NPBC amended to include topotecan, gemcitabine (Gemzar) or any other drug approved in this setting.
After three treatment cycles, the global health status and QOL score worsened significantly in the experimental arm (P = 0.003), but after six cycles this effect disappeared (P = 0.46). Adverse effects were slightly worse in the experimental arm, and included more neutropenia, musculoskeletal symptoms, and neuropathy. Participants in the standard arm reported more severe nausea.
The study’s main limitations were the fact that it closed before the planned number of events, and treatment had to be amended when liposomal doxorubicin became unavailable.
Don Dizon, MD, of Rhode Island Hospital and the Warren Alpert Medical School of Brown University, both in Providence, said he agreed with the authors’ conclusions that “there is nothing is to be gained by using a non-platinum first in this population.” However, he also pointed out that “there was also no detriment seen either.”
Clinicians may prefer to use a platinum-based chemotherapy, but other factors can also come into play, including patient preference, he told MedPage Today.
“Ultimately, these data show that we need to make progress for women who relapse,” said Dizon, who was not involved in the study.
It’s also important to recognize that the study was stopped early, he added, noting that, “This certainly impacted stats and also might have compromised the results.”
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