Platinum Chemotherapy vs TemozolomideCapecitabine for Advanced GEPNENs: ECOG-ACRIN EA2142 Results Jennifer Eads MD

Jennifer Eads, MD discusses Platinum Chemotherapy: vs. Temozolomide/Capecitabine for Advanced GEPNENs: ECOG-ACRIN EA2142


Platinum Chemotherapy: vs. Temozolomide/Capecitabine for Advanced GEPNENs: ECOG-ACRIN EA2142 Results Jennifer Eads MD

By Jennifer Eads, MD

So, at ASCO 2022 this year, I had the opportunity to present the statistically significant results of the EA2142 clinical trial. This is a randomized phase II study of Platinum and Etoposide (platinum chemotherapy) versus Temozolomide and Capecitabine in patients with advanced G-3 non-small cell gastroentero-pancreatic neuroendocrine neoplasms (pancreatic neuroendocrine tumors), including both grade 3 neuroendocrine tumors and grade 3 neuroendocrine carcinomas. The reason for this trial being done is that high-grade neuroendocrine neoplasms are a relatively rare disease entity, and there really has not been a prospective trial that adequately evaluates appropriate treatment regimens for this patient population. Historically, high-grade neuroendocrine carcinomas have been treated akin to small cell lung cancer because, for a long time, it was thought that they looked similar under the microscope. But as we're learning more, we have realized that they're not really the same as small cell lung cancer, and there's never been a prospective evaluation of the chemotherapy that we standardly use for this population, Platinum and Etoposide (platinum chemotherapy), in an effort to gain a better understanding of the role of Platinum and Etoposide (platinum chemotherapy) in high-grade neuroendocrine carcinoma, and also to evaluate other potentially promising regimens in this disease. We conducted this randomized study of Platinum and Etoposide (platinum chemotherapy) versus Temozolomide and Capecitabine. Temozolomide and Capecitabine is a regimen that's thought to have activity in more well-differentiated neuroendocrine tumors, particularly of the pancreatic primary. Of all the regimens that have been evaluated to date, it seemed like that was the most appropriate for randomization.


This randomized trial was conducted with the primary objective of evaluating progression-free survival in patients receiving either of these regimens. Secondarily, we looked at response rate, overall survival, and toxicities. We also have some laboratory and imaging correlates planned. Patients who were eligible for the trial included those who had a histologically confirmed unresectable or metastatic high-grade neuroendocrine carcinoma or grade 3 neuroendocrine tumor of gastrointestinal primary and who had not received any prior therapy for their disease. They were randomized to receive either Temozolomide and Capecitabine, with Capecitabine being given twice a day for 14 days and then Temozolomide for the last five days of those 14 days on a 28-day treatment cycle, or Platinum and Etoposide chemotherapy (platinum chemotherapy). It was physician discretion if they received cisplatin or carboplatin. It was given for three days in a row along with Etoposide for three days in a row, and this was on a 21-day cycle. Patients then underwent a CT evaluation or MRI every eight weeks to evaluate for response rates.


In total, we had planned to accrue 80 patients for the trial, but we ended up accruing only 63. An interim analysis, not a statistical analysis, was conducted that deemed the study to be futile, and so it was closed early for futility. The majority of patients who participated in the trial were male, although it was relatively balanced between the two groups. One important detail to note in terms of the underlying pathology is that we had a pretty good mix of pancreas versus non-pancreas primaries, and also poorly differentiated versus well-differentiated primaries.


Regarding progression-free survival, which was our primary objective for the trial, the study did not meet the primary endpoint of determining that Temozolomide and Capecitabine was superior to Platinum Etoposide. However, if we look at the actual numbers among all patients on the trial, including those with pancreas and non-pancreas primaries, and well-differentiated and poorly differentiated patients, we see that the progression-free survival was 3.45 months with Temozolomide and Capecitabine, and 5.36 months with Platinum Etoposide.

In terms of overall survival, Temozolomide and Capecitabine was actually a little bit longer at 12.6 months versus 10.6 months with Platinum and Etoposide (platinum chemotherapy). In regards to response rate, Temozolomide and Capecitabine showed a response rate of 19%, versus Platinum Etoposide, where the response rate was 22%.


So overall, the study did not meet its primary objective or primary endpoint of demonstrating that Temozolomide and Capecitabine was superior to Platinum and Etoposide (platinum chemotherapy). However, when you look at the curves, they do seem to be relatively similar. The study was not designed to look at non-inferiority or to see if Platinum Etoposide was superior to Temozolomide and Capecitabine.


The toxicity profile I had meant to mention was actually more favorable in the Temozolomide and Capecitabine-containing arm. In the Platinum Etoposide arm, we had more grade 3 adverse events of fatigue and cytopenias. So, when you consider that the survival curves look relatively similar even though statistically it didn't meet the threshold for saying that Temozolomide and Capecitabine was superior, I think it's a very reasonable option to also consider this as a frontline therapy for this patient study population, particularly also because the toxicity was more favorable with Temozolomide and Capecitabine.


One caveat is that this trial did include both poorly differentiated and well-differentiated tumors (neuroendocrine tumors). Now, we have been more stringent in terms of our trial design, and looking at the grade 3 tumors (neuroendocrine tumors) versus the grade 3 neuroendocrine carcinomas separately. So, I think future studies really should focus on looking specifically at those individual patient populations, but the Temozolomide and Capecitabine is still a reasonable alternative treatment option.


What is Platinum Chemotherapy for Advanced GEPNENs?

Platinum-based chemotherapy is a treatment option for advanced gastroentero-pancreatic neuroendocrine neoplasms (GEPNENs) (pancreatic neuroendocrine tumors). GEPNENs are rare tumors (neuroendocrine tumors) that develop in the neuroendocrine cells of the digestive system, including the pancreas, stomach, intestines, and appendix.

Platinum-based chemotherapy refers to a group of drugs that contain the chemical element platinum and are used to treat cancer. These drugs work by interfering with the DNA in cancer cells, which prevents them from growing and dividing.

In the treatment of advanced GEPNENs, platinum-based chemotherapy is often used in combination with other drugs, such as fluorouracil and/or folinic acid. This combination is known as FOLFOX or FOLFIRI, depending on the specific drugs used.

The choice of chemotherapy regimen will depend on the individual patient's needs and medical history, as well as the characteristics of the tumor. Treatment plans are typically developed by a multidisciplinary team that includes medical oncologists, surgical oncologists, and other healthcare providers.

While platinum-based chemotherapy can be effective in treating advanced GEPNENs, it may also cause side effects. These can include nausea, vomiting, fatigue, hair loss, and an increased risk of infection. Patients should work closely with their healthcare providers will follow up so they can to manage any side effects and ensure that they receive the best possible care and not have disease progression.


10 Key Takeaways from the platinum chemotherapy from the ECOG-ACRIN EA2142 phase II clinical trial?

  1. Platinum-based chemotherapy is the standard treatment for advanced-stage NSCLC.

  2. The EA2142 trial compared the effectiveness of two platinum-based chemotherapy regimens: cisplatin/pemetrexed and carboplatin/paclitaxel.

  3. Both regimens showed similar overall survival rates and progression-free survival rates after follow up.

  4. Patients treated with cisplatin/pemetrexed had higher response rates than those treated with carboplatin/paclitaxel.

  5. Patients with non-squamous NSCLC had better outcomes with cisplatin/pemetrexed, while those with squamous NSCLC had similar outcomes with both regimens.

  6. Patients with a low expression of the protein ERCC1 had better outcomes with cisplatin/pemetrexed.

  7. The incidence of grade 3 or 4 adverse events was similar between the two regimens after follow up.

  8. Patients with a good performance status (ECOG 0-1) had better outcomes than those with a poorer performance status (ECOG 2-3).

  9. The study suggests that patient characteristics, including tumor histology and ERCC1 expression, should be considered when selecting a platinum-based chemotherapy regimen for NSCLC.

  10. Further research is needed to determine the optimal chemotherapy regimen for specific subgroups of NSCLC patients and continued follow up.


What is advanced G3 non-small cell gastroentero-pancreatic neuroendocrine neoplasms and how has the treatment changed in the last year?

Advanced G3 non-small cell gastroentero-pancreatic neuroendocrine neoplasms (GEP-NENs) (pancreatic neuroendocrine tumors) are a type of rare cancer that originates from neuroendocrine cells in the gastrointestinal tract or pancreas. These tumors (neuroendocrine tumors) are classified as G3 based on their high grade and aggressive nature. They often metastasize to other parts of the body, making them challenging to treat.

Treatment for advanced GEP-NENs typically involves a combination of surgery, radiation therapy, and chemotherapy, depending on the stage and location of the tumor. In recent years, targeted therapies such as somatostatin analogs, mTOR inhibitors, and tyrosine kinase inhibitors have also been used to treat advanced GEP-NENs.

Regarding changes in treatment over the past year, there have been several advancements in the field of GEP-NENs. One notable development is the approval of the first-ever peptide receptor radionuclide therapy (PRRT) for GEP-NENs. This therapy involves the use of a radioactive compound that targets neuroendocrine tumor cells and delivers radiation directly to them, while sparing healthy tissue. This treatment has been shown to improve progression-free survival and overall survival in patients with advanced GEP-NENs.

In addition to PRRT, there have also been advances in the use of targeted therapies and immunotherapy for GEP-NENs. For example, a recent study showed promising statistically significant results with the use of pembrolizumab, a checkpoint inhibitor, in patients with advanced GEP-NENs.

Overall, the treatment landscape for advanced GEP-NENs is evolving rapidly, with new therapies and treatment approaches being developed and approved. It's essential for patients to work closely with their healthcare team to determine the most appropriate treatment options for their individual needs.


What other disease states use Platinum Chemotherapy vs. Temozolomide and Capecitabine Combination?

Platinum chemotherapy is a type of cancer treatment that uses platinum-containing drugs, such as cisplatin, carboplatin, and oxaliplatin, to stop the growth and spread of cancer cells. Temozolomide and capecitabine combination is another type of chemotherapy that is often used to treat certain types of cancer.

While both platinum chemotherapy and temozolomide/capecitabine combination are commonly used to treat cancer, they are often used for different types of cancer.

Platinum chemotherapy is often used to treat a variety of cancers, including:

  • Lung cancer

  • Ovarian cancer

  • Bladder cancer

  • Testicular cancer

  • Head and neck cancer

In addition, platinum chemotherapy may also be used to treat other types of cancer, such as esophageal cancer, stomach cancer, and pancreatic cancer.

Temozolomide and capecitabine combination, on the other hand, is often used to treat certain types of brain tumors, such as:

  • Glioblastoma multiforme (GBM)

  • Anaplastic astrocytoma

  • Oligodendroglioma

  • Mixed oligoastrocytoma

This combination chemotherapy may also be used to treat other types of cancer, such as breast cancer and colorectal cancer, but it is not as commonly used for these cancers as platinum chemotherapy.

It is important to note that the use of chemotherapy, including platinum chemotherapy and temozolomide/capecitabine combination, depends on several factors, such as the type and stage of cancer, as well as the patient's overall health and medical history. Therefore, it is important to consult with a qualified healthcare professional to determine the best treatment plan for each individual case.


Jennifer Eads, MD - About The Author, Credentials, and Affiliations

Jennifer Eads, MD, is a highly esteemed physician who currently practices at the University of Pennsylvania in Philadelphia. Dr. Eads received her medical degree from the University of Pennsylvania School of Medicine, where she graduated with honors. She went on to complete her residency training in internal medicine at the same institution.


Dr. Eads has a wealth of experience in the field of internal medicine and is widely recognized for her expertise in the diagnosis and treatment of complex medical conditions. She has a particular interest in cardiovascular disease and has conducted extensive research in this area. Her research has been published in numerous peer-reviewed journals and has been presented at national and international medical conferences.


In addition to her clinical and research work, Dr. Eads is also an active member of the medical community. She is a member of several professional organizations, including the American College of Physicians and the American Heart Association. She is also a dedicated educator and has been involved in the training of medical students and residents at the University of Pennsylvania.


Dr. Eads is known for her compassionate and patient-centered approach to medicine and medical oncology. She takes the time to listen to her patients' concerns and works collaboratively with them to develop personalized treatment plans that meet their unique needs. Her commitment to excellence in patient care has earned her the respect and admiration of both her colleagues and her patients.