乌鸦传媒

New and emerging approaches to treat cancer were reported this week at the in Dublin, Ireland, cosponsored by the European Organization for Research and Treatment of Cancer, the National Cancer Institute, and the American Association for Cancer Research. Notable presentations at the meeting included the studies summarized below.

Genomic Tests May Aid Treatment Decisions

Breast cancers that had genetic signatures associated with "ultra-high risk" were more than twice as likely to respond completely to preoperative targeted agents and/or chemotherapy as compared with lower-risk tumors.

After adjustment for hormone (HR) and HER2 receptor status, 483 tumors at ultra-high risk by the 70-gene MammaPrint assay (MP2) had an odds ratio for pathologic complete response of 2.43 as compared with 503 MP1 tumors. HR+ tumors that were also MP2 were more than three times as likely (3.62 for HER2-, 3.2 for HER2+) to respond to neoadjuvant treatment, reported Laura van 't Veer, PhD, of the University of California San Francisco.

Additional analyses identified several drugs and combinations had increased the odds of achieving pCR: veliparib/carboplatin, neratinib (Nerlynx), ganitumab, TDM1 (Kadcyla)/pertuzumab (Perjeta), and pembrolizumab (Keytruda) in addition to paclitaxel with or without trastuzumab (Herceptin).

A study evaluating the 80-gene BluePrint assay categorized breast tumors in 981 patients to one of three intrinsic subtypes: luminal, HER2, and basal. Previous studies showed the assay subtypes predicted response to neoadjuvant chemotherapy and HR+/HER2+ HER2-type tumors were more likely to respond to HER2-targeted therapy than were HR+/HER2+ luminal-type tumors.

The principal analysis focused on 375 patients with HR+/HER2- tumors, of whom 108 (29%) had basal-type gene signatures. Evaluation of responses to seven different treatment arms showed that basal-type HR+/HER2- tumors were four to five times as likely to achieve pCR with neoadjuvant chemotherapy.

Both studies involved patients enrolled in the ongoing .

Rare GI Tumor Responds to Combination

More than 40% of patients with two types of rare, incurable gastrointestinal tumors responded to treatment with the targeted combination of dabrafenib (Tafinlar) and trametinib (Mekinist).

The total response rate (42.8%) included 13 of 32 patients with biliary tract cancer and two of three patients with adenocarcinoma of the small intestine. All of the patients had tumors with the BRAF V600E mutation targeted by the drug combination.

The treatment resulted in a median progression-free survival of 7.2 months (PFS) and overall survival of 11.3 months. Several patients had PFS exceeding a year and overall survival exceeding 2 years, reported Zev Wainberg, MD, of the University of California Los Angeles.

The two tumors represented in the trial affect one to two people in 100,000 and have very poor prognosis, associated with a 5-year survival <5%. Wainberg said 78% of patients in his study had disease progression with two or more prior chemotherapy regimens.

Combination Active in Limited-Mutation Cancers

A preliminary trial of involving patients with advanced solid tumors provided evidence of antitumor activity with an immunotherapy-based combination microsatellite-stable (MSS) colorectal cancer, which has proven resistant to most immunotherapies.

The study involved a total of 16 patients with various types of advanced cancer, including five patients with colorectal cancer. The combination of the PD-1 inhibitor nivolumab (Opdivo) and pixatimod, which targets dendritic cells and natural killer cells, led to objective responses in two of the patients with colorectal cancer and stable disease in a third. A fourth patient with advanced colorectal cancer remained on treatment despite not meeting criteria for response or stable disease, reported James Kuo, MD, of Scientia Clinical Research in Sydney, Australia.

Gene expression profiles of the tumors showed that the four patients who benefited from the combination had MSS tumors, which have relatively few mutations emitting signals to the immune system. To date studies have shown little antitumor activity with single-agent immune checkpoint inhibitor therapy in MSS colorectal cancer, said Kuo. Combining a checkpoint inhibitor with a drug such as pixatimod, which stimulates other components of the immune system, may help overcome MSS tumors' relative lack of responsiveness to immunotherapy.

Investigational Drug Duo Slows Lung Cancer

An investigational immunotherapy combination achieved at least stable disease in more than half of patients with advanced non-small cell lung cancer.

A study of 25 patients with progressive disease showed objective responses in two and stable disease in another 12 with the combination of the anti-adenosine drug NIR178 and the PD-1 inhibitor spartalizumab. Among 14 patients with no prior exposure to anti-PD-1/PD-L1 therapy, the combination achieved one complete response, one partial response, and stable disease in six patients. Additionally, six of 11 patients previously treated with an anti-PD-1/PD-L1 agent had stable disease during treatment with the combination, reported Alberto Chiappori, MD, of the Moffitt Cancer Center in Tampa, Florida.

Explaining the rationale for combining the two drugs, Chiappori pointed out that adenosine is one of multiple molecules that tumors can recruit from the microenvironment to evade or suppress the immune system. Inhibiting or neutralizing adenosine removes a key tumor defense mechanism against immune-based anticancer strategies.