Even at Stage IV, Immunotherapy Helps in Pancreatic Cancer

CHICAGO -- Real-world data demonstrate that immunotherapies, broadly defined, prolong survival in stage IV pancreatic cancer compared with standard care, a researcher said here.

Records from the U.S. National Cancer Database (NCDB) from 2004 to 2018, including 827 patients with pancreatic adenocarcinomas treated with passive or active immunotherapy and 188,290 receiving standard care, show a 1-year overall survival (OS) rate of 42.3% among the former versus 17.2% with other treatment (P<0.001), according to Yi Jiang, MD, of Cedars-Sinai Medical Center in Los Angeles.

OS rates at 3 and 5 years also differed significantly, Jiang reported at Digestive Disease Week (DDW):

• 3-year: 8.8% vs 3.4% (P<0.001)
• 5-year: 3.6% vs 2.0% (P<0.001)

Along these lines, median OS also favored immunotherapy at 10 months compared with 3.4 months for chemotherapy (P<0.001).

These data, with fewer than 1,000 patients receiving immunotherapy over the study's 15-year timeframe, suggest that immunotherapies are underutilized in pancreatic cancer. But they also confirm yet again that, almost irrespective of treatment, stage IV pancreatic cancer remains highly lethal in the long term.

Immunotherapies for cancer can take many forms, Jiang explained. Like other tumor types, pancreatic adenocarcinoma tumors feature multiple defense mechanisms against host immune attack. They release signalling molecules that tell host immune cells to stand down; they produce proteins that induce those cells to commit suicide; they shield themselves with biofilms to evade surveillance and/or block penetration by immune cells. Drugs to defeat each of these mechanisms are now available or in development.

The NCDB, a joint project of the American Cancer Society and the American College of Surgeons, defines immunotherapy to also include synthetic antibodies -- e.g., trastuzumab (Herceptin) and cetuximab (Erbitux) -- which exploit immune-system biology to attack tumors directly. In total, Jiang listed 23 different agents as included in the NCDB's definition.

Jiang noted in her DDW talk that 52% of pancreatic cancer cases are diagnosed when they have already metastasized, at which point only about 3% of patients are still alive 5 years after diagnosis. She cited an earlier study that found that patients with less advanced, resectable ductal adenocarcinomas did somewhat better with adjuvant immunotherapy versus other treatment, with median OS of 29 versus 24 months. That led her to examine whether the same might be true for stage IV disease.

They drew on the NCDB, which Jiang said captures about 72% of all cancer cases. They focused on adult patients with ICD codes for pancreatic ductal adenocarcinoma, at stage IV under American Joint Committee on Cancer criteria.

The "average" patient receiving immunotherapy differed in many respects from his/her counterpart treated otherwise: younger on average by about 5 years, and more likely male, white, educated, more affluent, privately insured, and receiving care at an academic institution. Also, 71% of immunotherapy patients were diagnosed after 2012, whereas that was the case for half of the chemotherapy patients.

Perhaps most notably, "standard care" did not always involve cytotoxic chemotherapy. Only 53% of the non-immunotherapy group received it, as compared with 92% of those given immunotherapies. In fact, it appeared that nearly half of the standard-therapy group received only palliative/supportive care (i.e., no chemotherapy or radiation).

Jiang and colleagues adjusted for all these variables in their statistical modelling. Their estimates of median survival came with relatively narrow confidence intervals: 9.99 months for immunotherapy (95% CI 9.17-10.81) and 3.42 months for standard care (95% CI 3.39-3.45).

Similarly, the hazard ratio for death through 5 years was 0.73 (95% CI 0.67-0.80) with immunotherapy versus standard care.

Limitations to the analysis included lack of data on other potential confounders, such as baseline performance status or the time course of therapy. Survival without disease progression is also not tracked in the NCDB. The analysis also did not indicate whether any particular types of immunotherapy contributed more than others to the improved survival.

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