木瓜直播

Site-specific therapy guided by gene-expressing profiling (GEP) could improve outcomes for patients with previously untreated cancers of unknown primary (CUP), Chinese researchers suggested.

In their single-center randomized trial of patients with unfavorable CUP, GEP-guided site-specific therapy significantly improved progression-free survival (PFS) compared with standard empirical chemotherapy (9.6 vs 6.6 months, respectively; HR 0.68, 95% CI 0.49-0.93, P=0.017), reported Xichun Hu, MD, PhD, of the Fudan University Shanghai Cancer Center, and colleagues.

Overall survival favored the site-specific therapy arm, but the difference was not statistically significant (28.2 vs 19 months; HR 0.74, 95% CI 0.52-1.06, P=0.098), according to findings published in .

"Our trial is the first randomized study showing that using a primary site classifier based on gene-expression profiling improves prognosis for patients with CUP," wrote Hu and colleagues. "Our findings suggest that identifying the tissue of origin as a guide for site-specific therapy has the potential to be the new standard of care in patients with CUP in the era of precision medicine."

Coupled with the findings from the randomized , GEP-guided therapy "should emerge as a new standard of care" for unfavorable CUP, agreed F. Anthony Greco, MD, of the Sarah Cannon Research Institute and Cancer Center in Nashville, Tennessee, and colleagues, writing in an .

"This pivotal trial emphasizes the importance of GEP in helping to improve the management of patients, notably when coupled with adequate delivery of [molecularly guided therapy] or immunotherapy-based regimens according to tissue of origin," wrote Greco and co-authors. "The use of site-specific therapy guided by GEP should be recommended and has relevance for patients with molecularly diagnosed cancers now requiring precision site-specific therapy rather than empirical chemotherapy."

CUP is a rare, pathologically diagnosed metastatic cancer where the origin of the cancer is unknown. According to the American Cancer Society, roughly 35,000 cases of CUP will be diagnosed in the U.S. this year. Standard upfront treatment of platinum-based empirical chemotherapy is associated with poor survival outcomes.

The from Hu and colleagues included 182 patients with CUP (58% male, 42% over 60 years of age, all Asian) who were randomly assigned to either site-specific therapy or empirical chemotherapy from September 2017 to March 2021 at the Fudan University Shanghai Cancer Center.

A 90-gene expression assay that uses differential gene-expression patterns to assign tumors to one of 21 tumor types in its spectrum was applied to predict the tissue of origin for 83 of the 91 patients in the site-specific therapy group.

The most common predicted primary sites were gastroesophageal, lung, ovary, cervix, and breast, accounting for about 60% of all patients with CUP in the site-specific therapy group. Other predicted primary sites included head and neck, urinary, pancreas, colorectal, germ cell, liver/cholangiocarcinoma, mesothelioma, neuroendocrine, and kidney.

About a fourth of the patients in the site-specific therapy group received the same regimen as listed for the empirical chemotherapy group, while 45% received targeted agents or immunotherapy.

In their commentary, Greco and colleagues noted that "only a minority of patients (eight of 31) with predicted cancer types that would be expected to respond favorably to immunotherapy actually received standard immunotherapy," suggesting that "the results of this trial would likely be even more impactful had more of these patients received immunotherapy."

In addition to the results described above, objective response rates were numerically higher with site-specific therapy (49% vs 46% with empirical chemotherapy).

Among the 167 patients who started their planned treatment, 56% in the site-specific therapy group and 61% in the empirical chemotherapy group had grade ≥3 treatment-related adverse events, the most frequent of which were decreased neutrophil counts (44% vs 49%, respectively), decreased white blood cell count (21% vs 26%), and anemia (12% vs 11%).

Treatment-related serious adverse events were reported in 6% of patients in the site-specific therapy group and 2% of those in the empirical chemotherapy group.

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