The Best Results Yet in Pancreatic Cancer Treatment

Advanced pancreatic cancer patients were included in a small clinical trial, which found that adding a third chemotherapy to the currently standard doublet significantly supported tumor shrinkage and overall survival.

In the study, the standard treatment for advanced pancreatic cancer, nab-paclitaxel plus gemcitabine, was supplemented with cisplatin .

One of the trial’s lead authors, Gayle Jameson, said, "Both median progression-free survival and overall survival were almost twice what we could achieve with standard doublet chemotherapy, so we believe we have made real progress in this disease," she said.

We know pancreatic cancer cells have DNA repair problems , and current standard treatment did not target this vulnerability. Cisplatin can target cells with DNA repair problems, which may explain why it worked.

The study was published on 3 October 2019 in Journal of the American Medical Association (JAMA) Oncology’as a journal publication.

The researchers named this triplet triple-drug regimen ('TGen Triple') .

Details of the results

The study enrolled patients with a median age of 65 who had not previously received treatment, a total of 25 with advanced pancreatic cancer.

Most patients (76%) initially had elevated CA19-9 levels, and subsequently this tumor marker was measured to monitor 18 patients.

All patients received chemotherapy on days 1-8, every 21 days, at the following doses:

• nab-paclitaxel 125 mg/m2
• gemcitabine 1000 mg/m2 and
• cisplatin (one of these 3 doses: 25 mg/m2; 37.5 mg/m2 or 50 mg/m2)

The maximum tolerated cisplatin dose was found to be 25 mg/m2.

Patients also received aggressive hydration (fluids) on days 2 and 9 of each cycle, and subcutaneous pegfilgrastim on day 9 of each cycle (to preventleukopenia and neutropenia ).

Median treatment duration was 8 courses / cycles, and nearly one-third of the group received treatment for at least 6 months.

• Among 24 evaluable patients, the objective response rate was 71% in the study. 
• Two patients (8%) were reported to achieve a complete response and 15 (62%) a partial response. 
• The researchers reported stable disease in four other patients (17%), while three patients (12%) had progressive disease.
• Of 24 patients, 16 (64%) were alive at 1 year, and 10 (40%) at 2 years.
• At year 3, four patients (16%) were still alive, and one (4%) was reported to have survived more than 4 years.

Comparison with previous study results

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Historically, overall survival in advanced pancreatic cancer without treatment ranged from 3 to 6 months.

With gemcitabine, the first drug approved for advanced pancreatic cancer, this approached approximately 7 months.

Nab-paclitaxel plus gemcitabine then extended overall survival to 8.5 months. Subsequently, FOLFIRINOX brought it to 11 months.

Now, with the triplet drug regimen used in this study, median overall survival was 16.4 months. Median progression-free survival was 10.1 months, and at 9-week follow-up the disease control rate was 88%.

Side effects

Serious treatment-related side effects (grade 3 or higher) were mostly hematological (blood-related): 68% developed thrombocytopenia, 32% anemia and 24% neutropenia.

Fatal events occurred among 24 patients in three (12%), with two judged related to trial participation.

Although hematological side effects were frequent, most adverse events required no clinical intervention and treatment tolerability was acceptable; nearly two-thirds of patients completed full-dose treatment for 3 or more cycles.

The high objective response rate reported is among the highest observed in phase 1b / 2 pancreatic cancer trials.

The researchers also noted that most patients with initially elevated CA19-9 levels showed rapid decreases in CA19-9, consistent with radiological findings of reduced tumor size.

However, the results of this small clinical trial require confirmation in a larger phase-3 study. Metastatic pancreatic cancer is now the focus of an ongoing phase-3 study of this triplet regimen.