Pancreatic Cancer Research Highlights from ASCO Annual Meeting

Pazit Polak; Wikimedia

The American Society of Clinical Oncology (ASCO) Annual Meeting is the premier global gathering of the top minds in oncology research and treatment.

This year’s meeting was held May 29th to June 2nd in Chicago. Although this meeting focuses on all cancers, pancreatic cancer was well represented. Here are just some of the encouraging findings from ongoing pancreatic cancer clinical trials showcased during the event. As always, Let’s Win will cover several of these and others in more depth in the coming months.

Tumor-Treating Fields Improve Overall Survival

Final results of the phase III PANOVA-3 trial show small but statistically significant gains in overall survival in patients with locally advanced pancreatic cancer. In the trial, patients who were given the combination of tumor treating fields added to gemcitabine and nab-paclitaxel in first-line therapy had an improvement of two months in overall survival compared with gemcitabine/nab-paclitaxel alone.

The trial is the first to demonstrate a statistically significant overall survival benefit in locally advanced pancreatic cancer, the researchers said. The addition of tumor-treating fields to first-line chemotherapy can not only extend overall survival, but it does so without increasing systemic toxicity among patients. Patients who received tumor-treating fields plus chemotherapy also experienced prolonged pain-free survival and distant progression-free survival compared with those who received chemotherapy alone.

The researchers say additional data on quality-of-life issues will be very important moving forward. A pilot study, PANOVA-4, is currently underway in Europe to evaluate the effects of adding atezolizumab immunotherapy to tumor-treating fields/gemcitabine-nab-paclitaxel as a first-line treatment for patients with metastatic pancreatic cancer.

Another Combination for Resectable and Borderline Resectable Disease

For patients with resectable or borderline resectable pancreatic cancer, neoadjuvant treatment with a combination of cisplatin (P), nab-paclitaxel (A), capecitabine (X), and gemcitabine (G), known as PAXG, improved event-free survival compared with the modified FOLFIRINOX (mFOLFIRINOX) regimen (fluorouracil, irinotecan, and oxaliplatin), according to results from the phase III CASSANDRA trial.

Results of the study showed that after a median follow up of 24.5 months in the PAXG group and 26 months in the mFOLFIRINOX group, the PAXG regimen was associated with a median event-free survival of 16 months, compared with 10.2 months with mFOLFIRINOX. Event-free survival means an absence of the following: disease progression, recurrence, two consecutive CA 19-9 increases of 20 percent or more separated by at least four weeks, unresectability, intraoperative metastasis, or death.

Possible Treatment for Chemotherapy-Induced Thrombocytopenia

Chemotherapy‑induced thrombocytopenia (CIT) is an unfortunate common adverse event that can negatively affect care by postponing treatment. Now, results from the phase III RECITE trial show that a drug called romiplostim is effective in treating it in patients with a gastrointestinal cancer who are receiving oxaliplatin-based chemotherapy.

The RECITE trial enrolled patients receiving oxaliplatin‑based treatment for GI cancers with persistent CIT at 55 sites across 14 countries. The majority of patients enrolled in the trial had colorectal cancer (75 percent); the remainder had gastroesophageal (13 percent) or pancreatic (12 percent) cancer. Investigators randomly assigned 109 individuals to receive romiplostim and 56 individuals to receive a placebo for three chemotherapy cycles. The primary endpoint for the trial was the rate of CIT‑induced dose modifications.

At the end of three cycles, 84.4 percent of patients who were given romiplostim avoided chemotherapy dose modifications compared with 35.7 percent in the placebo group. The romiplostim cohort also had significantly higher platelet count nadirs and a faster median time to response, with no treatment-related serious adverse events. Further analysis showed 75.5 percent of individuals receiving romiplostim achieved a relative dose intensity of 85 percent or higher versus just 38.2 percent of patients in the placebo group.

The researchers wrote: “These results are potentially practice‑changing for a common serious condition encountered routinely in clinical practice worldwide that prevents delivery of on-time, full-dose anticancer therapy. Final results from long‑term follow-up will be presented.”

 Mapping Pelareorep’s Immune Activation Capabilities

The GOBLET study is investigating pelareorep, an oncolytic reovirus, in combination with other therapies for pancreatic cancer, colorectal cancer, and anal cancer. The phase I/II, open-label, non-randomized study assesses the safety and efficacy of pelareorep, which has shown promise in increasing the activity of the patient’s immune system against tumors. 

Its developer, Oncolytics Biotech Inc., (Calgary, Alberta, Canada) highlighted new data from the study in a poster presentation showing pelareorep’s mechanism of action in pancreatic cancer. Researchers say this offers new insights into how this immunotherapy stimulates multiple arms of the immune system and primes tumors for treatment.

Pelareorep initiates a pro-inflammatory tumor microenvironment and induces innate and adaptive immune responses, according to data presented. New analyses confirm that pelareorep primes the tumor microenvironment to allow circulating tumor-infiltrating lymphocytes in the blood to attack the tumor.

“For the first time, we’re able to map the cascade of immune responses stimulated by pelareorep,” said Thomas C. Heineman, M.D., Ph.D., Chief Medical Officer for Oncolytics Biotech in a statement. “It starts with the expansion of anti-reovirus T cells, followed by the upregulation of chemokines that mediate the expansion of pre-existing TIL clones in the blood. These T cells can now return to the tumor and attack it, resulting in a reduction in tumor size.

“Pelareorep-mediated upregulation of chemokines also makes the tumor microenvironment immunologically active and able to actively recruit cancer-specific T cells to the tumor. These findings deepen our understanding of pelareorep’s ability to convert immunologically cold tumors into immunologically active ones that may benefit from pelareorep-based combination therapy.”

Neo-Epitope Vaccine Shows Promise

Tedopi (OSE-2101) is a neo-epitope-based therapeutic cancer vaccine developed by the French biotech company OSE Immunotherapeutics. The vaccine is composed of a combination of 10 optimized neo-epitopes derived from five tumor-associated antigens. These neo-epitopes are parts of proteins that are structurally altered in cancer cells and can trigger a strong immune response against them. Tedopi works by stimulating cytotoxic T cells to recognize and eliminate cancerous cells. 

The vaccine is currently being investigated in a phase II clinical trial called TEDOPaM for patients with advanced or metastatic pancreatic cancer. Positive topline results presented at ASCO highlighted that the study met its primary endpoint, showing a 12-month overall survival rate of 65 percent in the group treated with Tedopi and FOLFIRI chemotherapy. Two complete responses were observed in the Tedopi arm, while none were seen in the control arm (FOLFIRI alone). The addition of Tedopi demonstrated minimal toxicity, with only six percent of serious adverse events deemed vaccine-related.