Philip A. Philip, MD, PhD, FRCP, professor of medicine, Wayne State University School of Medicine, clinical professor of oncology at Barbara Ann Karmanos Cancer Institute, discusses adverse events (AEs) associated with Lutathera (lutetium Lu 177 dotatate) in neuroendocrine tumors (NETs).

Prior to the FDA approval of Lutathera, there were no systemic therapies that would lead to tumor shrinkage, says Philip. Now, approximately 20% of patients will experience tumor shrinkage with this therapy. Furthermore, many patients will achieve stable disease for a long time. In the phase III NETTER-1 trial, which served as the basis for the agent’s approval, the progression-free survival curves show a significant separation.

However, among the notable AEs observed with the peptide receptor radionuclide therapy (PRRT) is bone marrow suppression. There is also a risk of myelodysplasia or even leukemia; this can damage the kidneys. Although this damage can be counteracted by infusing amino acids, nausea and vomiting typically ensue, explains Philip. Lutathera is the first effective systemic therapy available to patients, but it does not signal the end of research regarding its use. In doing more research with regard to patient selection, sequencing, and potential combination partners, quality of life will have to be kept in mind, as most patients with NETs can lead an otherwise normal life.

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Dr. Philip on Adverse Events With Lutathera in NETs

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the use of Lutathera (lutetium Lu 177 dotatate) in neuroendocrine tumors (NETs).

The peptide receptor radionuclide therapy Lutathera is a relatively new treatment option in the United States. The therapy was approved by the FDA in January 2018 as a result of the phase III NETTER-1 study. The treatment targets the somatostatin receptor, which is expressed in approximately 80% to 90% of patients who have well-differentiated NETs. However, patients with poorly differentiated NETs may also express it, Philip notes.

Traditionally, the somatostatin analogs octreotide (Sandostatin) and lanreotide (Somatuline Depot) have been used to target the somatostatin receptor, but Lutathera now represents another option in this setting. By attaching a radioactive payload to the ligand that binds to the somatostatin receptor, the therapy can kill the cancer cells, Philip says.

Lutetium-177 is the active radioactive isotype in Lutathera. Lutathera is given systemically as 4 treatments, 2 months apart. The treatment itself is given intravenously over a course of 30 minutes, says Philip.

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the use of Lutathera in neuroendocrine tumors.

Dr. Philip Discusses the Use of Lutathera in NETs

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the impact of the PRODIGE 24/CCTG PA.6 study in pancreatic cancer.

In this phase III study, the use of modified FOLFIRINOX resulted in a significantly better overall survival and disease-free survival (DFS) compared with gemcitabine alone. DFS served as the primary endpoint of the study. These data were the first to demonstrate such a profound benefit with the use of adjuvant chemotherapy, Philip says. Notably, there was no use of radiation therapy in the study.

However, Philip notes, not all the patients were able to complete the full 6 months of therapy. This raises the issue of whether or not all patients are able to tolerate chemotherapy following surgical resection. Nonetheless, this was a good study showing that mFOLFIRINOX is improving the survival of patients with resectable disease, Philip concludes. Interestingly, patients treated with gemcitabine also did well on this study.

Philip A. Philip, MD, PhD, FRCP, professor, Department of Oncology, Karmanos Cancer Institute, discusses the impact of the PRODIGE 24/CCTG PA.6 study in pancreatic cancer.

Dr. Philip on the Impact of the PRODIGE 24/CCTG PA.6 Study in Pancreatic Cancer

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses research questions with Lutathera (lutetium Lu 177 dotatate) in the treatment of patients with neuroendocrine tumors (NETs).

For the first time, there is an effective therapy leading to tumor shrinkage in this patient population, but it does not mark the end of research, Philip says. There are still a number of unanswered questions in this space. Mainly, researchers are trying to determine the optimal patients to receive this therapy as well as where it should be sequenced in therapy. For example, should patients start with Lutathera right at diagnosis? At this point, physicians aren’t doing that, but there may be patients who benefit from this approach.

Another area of research is looking at combining Lutathera with other treatment modalities. Immunotherapy is a combination approach of interest because radiation has been shown to enhance immune response. Philip concludes that this is an exciting time for patients with NETs. Moving forward, researchers have to not only focus on prolonging survival but also maintaining the quality of life (QoL) for patients.

Philip A. Philip, MD, PhD, FRCP, professor, Department of Oncology, Barbara Ann Karmanos Cancer Institute, discusses research questions with Lutathera in the treatment of patients with neuroendocrine tumors.

Dr. Philip Discusses Research Questions With Lutathera in NETs

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the use of FOLFIRINOX in patients with locally advanced pancreatic cancer.

Over the last decade, adjuvant chemotherapy has undergone a significant improvement, Philip says. The field has seen evolution from single-agent gemcitabine to gemcitabine plus capecitabine to FOLFRINOX. Most recently, the PRODIGE 24/CCTG PA.6 trial study demonstrated a significant improvement in survival for patients with resectable pancreatic cancer treated with modified FOLFIRINOX (mFOLFIRINOX) versus gemcitabine.

Investigators designed the trial with mFOLFIRINOX, which does not include bolus IV 5-fluorouracil and is therefore less likely to result in hematologic toxicities and severe diarrhea. With these modifications, the regimen is better tolerated by patients, says Philip.

Philip A. Philip, MD, PhD, FRCP, professor, Department of Oncology, Karmanos Cancer Institute, discusses the use of FOLFIRINOX in patients with locally advanced pancreatic cancer.

Dr. Philip on FOLFIRINOX in Locally Advanced Pancreatic Cancer

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the importance of developing new drugs for patients with pancreatic cancer.

Unlike other chemotherapy-resistant cancers that have seen developments in treatments, pancreatic cancer is lacking beneficial improvements of other treatments, states Philip.

According to Philip, it is expected that pancreatic cancer will be the second leading cause of cancer mortalities by 2020. Most of the patients with pancreatic cancer have metastatic disease, making the only way to control the natural history of the disease is by getting better systemic treatments.

Philip A. Philip, MD, PhD, FRCP, professor of Medicine, Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses the importance of developing new drugs for patients with pancreatic cancer. 

Dr. Philip on the Importance of Developing New Drugs for Pancreatic Cancer

Philip A. Philip, MD, PhD, FRCP, professor of Medicine at Wayne State University School of Medicine, clinical professor of Oncology at Barbara Ann Karmanos Cancer Institute, discusses drug developments for patients with pancreatic cancer.

There has been a decade or more of pancreatic cancer research, with many of the trials resulting in negative outcomes, explains Philip. There was no patient population that reached a median survival of 12 months. All studies that focused on targeted agents failed to produce any clinically meaningful results regarding new treatment.

There is still much more availability of drugs than there was 5 years ago, says Philip. There are more studies being done about the biology and genetics of the disease, which helps develop new trials that could change the landscape of therapy.

Philip A. Philip, MD, PhD, FRCP

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