We had the pleasure of speaking with Manuel Hidalgo Medina, MD, PhD, chief of the Division of Hematology and Medical Oncology of Weill Cornell Medicine and NewYork-Presbyterian Hospital, to discuss some of the exciting research he presented at the 

 (PDOs) show promise for personalized therapy in patients with pancreatic cancer, said Dr. Hidalgo. Preliminary results from the HOPE trial demonstrated that PDOs may allow for the exclusion of ineffective drugs from combination regimens, thus reducing toxicity in patients with pancreatic cancer.

In the trial, investigators generated PDOs from patients with pancreatic cancer under real-world conditions to evaluate drug sensitivity against PDOs and correlate these data with clinical outcomes. Investigators estimated that a PDO AUC value of <1.66 yields a >99% probability of disease control from a regimen that contains a certain drug. They also found that if all drugs in a regimen had an AUC of >2.75 there is a >80% probability of accurately predicting resistance. In a patient with stage IV pancreatic ductal adenocarcinoma with a 

 mutation and ERBB2 amplification, the investigators were able to show the potential of PDO testing to tailor treatment. Specifically, the patient experienced disease control with FOLFIRINOX, which was held for toxicity. The PDO showed resistance to oxaliplatin and subsequently, the patient experienced an extended period of disease control with regimens that did not control the drug.

It is anticipated that this approach will be explored in future clinical trials to prospectively inform treatment selection for this patient population, said Dr. Hildago.

Additionally, Dr. Hidalgo also presented results from a phase 1b study which examined the use of palbociclib plus nab-paclitaxel in patients with metastatic adenocarcinoma of the pancreas (PDAC). In preclinical models, the combination was more effective than either agent alone and similar to that of palbociclib nab-paclitaxel plus gemcitabine. In the trial, investigators evaluated the safety, pharmacokinetics, pharmacodynamics, preliminary efficacy, and maximum tolerated dose of the doublet in patients with PDAC. Although the combination was found to be tolerable, with adverse events as expected based on the profiles of the single agents, the regimen did not meet the prespecified efficacy threshold, and thus, will not move forward.

In our exclusive interview, Dr. Hidalgo expanded on these studies and highlighted other exciting research being done in pancreatic cancer.

Videos

Manuel Hidalgo Medina, MD, PhD, discusses some of the exciting pancreatic cancer research presented at the 2020 ACCR Virtual Annual Meeting I.

Dr. Hidalgo Medina on Promising Research in Pancreatic Cancer

Manuel Hidalgo Medina, MD, PhD, chief, Division of Hematology and Medical Oncology, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses that rationale for using patient-derived organoids (PDOs) in pancreatic cancer.

In the HOPE study, investigators tested the use of PDOs to predict a patient’s response to treatment, says Hidalgo Medina. Results from the study indicated that PDOs could help personalize therapy for patients with pancreatic cancer and ultimately, spare them the toxicities that are associated with ineffective treatments.

In the trial, a patient’s response to standard therapy was correlated with the organoid’s response to the same treatment, explains Hidalgo Medina.

The correlation indicated that PDOs could have utility in informing treatment selection in patients with pancreatic cancer, says Hidalgo Medina. However, industrialization and standardization of PDOs is needed before the tool is made ready for clinical use.

Dr. Hidalgo Medina on the Rationale for Using Patient-Derived Organoids in Pancreatic Cancer

Manuel Hidalgo Medina, MD, PhD, chief, Division of Hematology and Medical Oncology, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses microsatellite instability (MSI) and germline testing patients with pancreatic cancer.

Patients should be tested for MSI upon diagnosis, explains Hidalgo Medina. There are indications that other molecular subgroups, such as NTRK fusions, get clear benefit from certain treatments, illustrating that all patients should receive germline testing upon diagnosis, as well. Knowing if patients harbor select biomarkers or mutations help physicians determine best standard of care or what clinical trials are most suited for patients.

Repeat MSI and germline testing, according to Hidalgo Medina, is not required. However, upon progression, it may be beneficial to rebiopsy the patient and sequence again to offer more opportunities for clinical trials, concludes Hidalgo Medina.

Manuel Hidalgo Medina, MD, PhD, discusses microsatellite instability and germline testing patients with pancreatic cancer.

Dr. Hidalgo Medina on MSI and Germline Testing in Pancreatic Cancer

Manuel Hidalgo Medina, MD, PhD, chief, Division of Hematology and Medical Oncology, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses treatment considerations in pancreatic cancer.

It is important to consider sequencing strategies when devising a treatment plan for patients with pancreatic cancer, says Hidalgo Medina. By sequencing systemic chemotherapy, patients will have the opportunity to derive the maximum benefit from treatment. In addition to sequencing strategies, it is also critical to evaluate 

 status, as the presence of the mutation could indicate that the patient is eligible to receive a PARP inhibitor, he adds.

Finally, it is important to remember that patients with reduced performance status can still derive benefit from systemic chemotherapy, says Hidalgo Medina. These patients should not be deemed ineligible for intensive therapy; rather, providers should aim to reduce their symptoms, which would potentially make them eligible for systemic therapy, concludes Hidalgo Medina.

Manuel Hidalgo Medina, MD, PhD, discusses treatment considerations in pancreatic cancer.

Dr. Hidalgo Medina on Treatment Considerations in Pancreatic Cancer

Manuel Hidalgo Medina, MD, PhD, chief, Division of Hematology and Medical Oncology, Weill Cornell Medicine/NewYork-Presbyterian Hospital, discusses the emergence of neoadjuvant chemotherapy and radiation in pancreatic cancer.

Traditionally, treatment for resectable pancreatic cancer involved surgery followed by adjuvant chemotherapy and, to some extent, that is still considered the standard of care; however, the field is moving towards neoadjuvant therapy, explains Hidalgo Medina. With patients who have disease that is a little larger than what is considered resectable, neoadjuvant chemotherapy and potentially radiation are used to achieve tumor shrinkage prior to surgery.

Neoadjuvant therapy is also likely beneficial in patients with resectable small disease and is the only option for patients with locally advanced disease that is not resectable. As chemotherapy becomes more effective and radiation becomes technically better, the pancreatic cancer field is going to move towards neoadjuvant chemotherapy; however, large, randomized clinical trials are still required, concludes Hidalgo Medina.

Manuel Hidalgo Medina, MD, PhD, discusses the emergence of neoadjuvant chemotherapy and radiation in pancreatic cancer.

Manuel Hidalgo Medina, MD, PhD

Articles

Dr. Hidalgo Medina on Promising Research in Pancreatic Cancer

Dr. Hidalgo Medina on the Rationale for Using Patient-Derived Organoids in Pancreatic Cancer

Dr. Hidalgo Medina on MSI and Germline Testing in Pancreatic Cancer

Dr. Hidalgo Medina on Treatment Considerations in Pancreatic Cancer

Dr. Hidalgo Medina on Neoadjuvant Therapy in Pancreatic Cancer