Pannaga G. Malalur, MBBS, medical oncology specialist, Gastrointestinal Cancers, The Ohio State University Comprehensive Cancer Center (OSUCCC) - James Cancer Hospital & Solove Research Institute, discusses several unmet needs within pancreatic cancer, including the implementation of updated germline genetic testing guidelines, increased screening of high-risk patients, and improved sequencing of available therapeutics.

In 2019, the National Comprehensive Cancer Network released updated guidelines for the use of germline and somatic testing, Malalur begins. Among other changes, these guidelines expanded the recommendation for germline genetic testing to all patients with pancreatic adenocarcinoma, rather than just those with a family or personal history of cancer, she explains.

However, a retrospective review presented at the 2023 ASCO Gastrointestinal Cancers Symposium found that the uptake rates and compliance for germline testing in clinical practice were low both 12 months before and after the updated guidelines were released, Malalur reports. These data not only show that guideline adherence is poor, but indicate that the overall use of germline genetic testing remains insufficient. Therefore, efforts to increase awareness of how genetic testing can allow for a personalized approach to treatment, the benefits of cascade testing, and opportunities for enrollment in pancreatic cancer surveillance programs continue to be necessary, according to Malalur.

Additionally, many patients with pancreatic cancer display high-risk clinical features that may preclude them from receiving aggressive treatment options, Malalur adds. These factors include advancing age, frailty, and comorbid conditions. Screening tools should be utilized to immediately assess the robustness of all patients and modify treatment approaches accordingly, Malalur says.

Lastly, the increase in novel actionable targets and available treatment options for patients with pancreatic cancer has substantially improved patient outcomes in pancreatic cancer, Malalur notes. However, this expansion has led to confusion regarding the navigation and selection of the optimal approach. Using next-generation sequencing could improve the identification of patients who would benefit from specific treatments, Malalur concludes.

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Pannaga G. Malalur, MBBS, discusses several unmet needs within pancreatic cancer, including the implementation of updated germline genetic testing guidelines, increased screening of high-risk patients, and improved sequencing of available therapeutics.

Dr Malalur on Addressing Unmet Needs in Pancreatic Cancer

Pannaga G. Malalur, MBBS, medical oncology specialist, Gastrointestinal Cancers, The Ohio State University Comprehensive Cancer Center (OSUCCC) - James Cancer Hospital & Solove Research Institute, discusses the implications of the findings for the use of liposomal irinotecan (Onivyde) plus 5-fluorouracil (5-FU), leucovorin, and oxaliplatin (NALIRIFOX) in the frontline setting for patients with metastatic pancreatic ductal adenocarcinoma (PDAC)

The phase 3 NAPOLI 3 trial (NCT04083235) evaluated the NALIRIFOX regimen nab-paclitaxel (Abraxane) plus gemcitabine in this patient population. Findings presented at the 

 showed a clinically meaningful and statistically significant improvement in both overall survival (OS) and progression-free survival (PFS) with NALIRIFOX. At a median follow-up of 16.1 months (95% CI, 15.3-16.8), a median OS of 11.1 months (95% CI, 10.0-12.1) was observed in the 383 patients treated with NALIRIFOX vs 9.2 months (95% CI, 8.3-10.6) for the 387 patients treated with nab-paclitaxel plus gemcitabine (HR, 0.83; 95% CI, 0.70-0.99; 

The median PFS was 7.4 months (95% CI, 6.0-7.7) and 5.6 months (95% CI, 5.3-5.8) for those treated with NALIRIFOX and nab-paclitaxel/gemcitabine, respectively (HR, 0.69; 95% CI, 0.58-0.83; 

Although safety data from the study demonstrated similar rates of grade 3 or higher treatment-emergent adverse effects (TEAEs) between the NALIRIFOX arm (87%) and the nab-paclitaxel/gemcitabine arm (86%), the AEs observed with NALIRIFOX varied from what was seen with standard of care chemotherapy, Malalur says. For example, patients treated with NALIRIFOX experienced a higher rates of gastrointestinal TEAEs, including nausea, vomiting, and diarrhea, and those treated with nab-paclitaxel plus gemcitabine experienced more cytopenias, Malalur explains.

The efficacy and safety data point to NALIRIFOX as a potential new first-line treatment option for patients with metastatic PDAC, and the varying TEAEs associated with the regimen and nab-paclitaxel/gemcitabine could allow for different choices for patients in this setting, Malalur concludes.

Pannaga G. Malalur, MBBS, discusses the implications of the findings for the use of liposomal irinotecan plus 5-fluorouracil, leucovorin, and oxaliplatin in the frontline setting for patients with metastatic pancreatic ductal adenocarcinoma.

Pannaga G. Malalur, MBBS

Articles

Dr Malalur on Addressing Unmet Needs in Pancreatic Cancer

Dr Malalur on the Implications of NALIRIFOX in Pancreatic Ductal Adenocarcinoma