George P. Kim, MD, recently shared the treatment considerations and decisions he makes when treating patients with metastatic pancreatic cancer. Kim, a medical oncologist at 21st Century Oncology in Jacksonville, Florida, explained his treatment decisions based on 2 case scenarios during a <em>Targeted Oncology</em> live case-based peer perspectives dinner.
George P. Kim, MD
George P. Kim, MD, recently shared the treatment considerations and decisions he makes when treating patients with metastatic pancreatic cancer. Kim, a medical oncologist at 21st Century Oncology in Jacksonville, Florida, explained his treatment decisions based on 2 case scenarios during aTargeted Oncologylive case-based peer perspectives dinner.
A 66-year-old female presented to her gastroenterologist with jaundice, weight loss, right upper quadrant abdominal pain, and diarrhea. She continued to carry out normal activity, but reported requiring rest on most days. Her CA 19-9 was 2296 U/mL. An abdominal CT scan showed an expansive mass lesion measuring 39 cm x 26 cm in the head of the pancreas. There were enlarged para-aortic lymph nodes and obstruction of the common bile duct.
Endoscopic retrograde cholangiopancreatography was performed, a stent was placed, and the patient was referred for surgery. Explorative laparotomy showed the mass to be inoperable because of local vascular infiltration and liver metastases. Pathophysiology confirmed pancreatic adenocarcinoma stage T4N1M1.
TARGETED ONCOLOGY: What is the patient’s prognosis?
Kim:This patient is unresectable, so the goal is palliation. In terms of months, the prognosis can be 1 to 1.5 years with locally advanced disease.
TARGETED ONCOLOGY: What factors need to be considered when determining the treatment plan for this patient?
Kim:With pancreatic cancer, it's always about performance statustheir appetite, pain control, biliary obstruction, intestinal obstruction, do they have blood clots? And then, what does the patient want. Does the patient want to be working, or does the patient have time off and not have to be concerned about that? Those are some of the considerations. Then we also consider what insurance the patient has, and things like that.
TARGETED ONCOLOGY: Discuss optimal supportive care for patients with metastatic pancreatic cancer.
Kim:Supportive care includes nutrition, pain, and diabetes control. You want to maintain the patient's [ECOG] performance status of 0 or 1.
How do you communicate with your patients regarding the goals of treatment? Choice of therapy? Toxicity profiles for available regimens?
Kim:I never make decisions as to what treatment a patient should be given. There are 2 standard therapies right now. One of them is FOLFIRINOX [folinic acid, fluorouacil (5-FU), irinotecan, and oxaliplatin] and the other is nab-paclitaxel [Abraxane] and gemcitabine. Both of them are palliative, so how do you communicate with the patient? The median survival is 11.1 months versus 8.7 months. Some people do much better than 11.1 months or 8.7 months, so you have to have a discussion about the median survival and what the trials have shown.
Then I get into more details about choice of therapy, and they are different. FOLFIRINOX is given every 2 weeks. You have to wear a pump, you're sick for several days after the treatment, and there is greater risk of neutropenia, diarrhea, nausea, and fatigue, so you may be out of function for up to 5 days. The other treatment is nab-paclitaxel/gemcitabine given weekly. Typically, it's easier to manage. Treatment is every week, so you can make adjustments as you go. Patients are out for 1 or 2 days, that's how I try to lay out the schedules. I try to let the patient decide which treatment is best for them.
Some patients have read up on the internet about FOLFIRINOX, and it can be quite toxic, so sometimes they avoid it because of what is written on the internet, even though it does have a higher survival11.1 versus 8.7 months.
Patients like this patient may not do well with FOLFIRINOX. They have a lot of symptoms, such as jaundice. It may be hard to give them irinotecan, which is in FOLFIRINOX. Similarly, it may be hard to give them nab-paclitaxel taxanes. You want to talk to patients and give them an opportunity to help them decide.
TARGETED ONCOLOGY: What are the options for systemic therapy?
Kim:There are 2 chemotherapies: FOLFIRINOX versus nab-paclitaxel/gemcitabine. There are also experimental trials. There are other treatments that may be available, such as radiation or burning liver lesions, things like that. There are other supportive measures that can be used.
The patient was started on gemcitabine plus albumin-bound (nab) paclitaxel. She complained of moderate nausea and fatigue for the first 4 weeks of therapy, which were managed with antiemetic therapy. Neutropenia was managed.
TARGETED ONCOLOGY: What are the supporting data for efficacy, safety, and quality of life with nab-paclitaxel?
Kim:The median survival is 8.7 months, progression-free survival is improved, response rates are parallel to what you get with FOLFIRINOX. The toxicities include neuropathy and low platelets. Quality of life is maintained.
TARGETED ONCOLOGY: How does the patient’s performance status (ECOG 1) impact your decision? What about age, comorbidities, gender and other issues?
Kim:If her performance status were a 2 or a 3that's when a patient is spending more time in bed and not being active—then you might start thinking about not giving chemotherapy or just giving gemcitabine by itself. For this patient who is ECOG 1, it is very reasonable. ECOG 0 is also very reasonable. Still, many people choose FOLFIRINOX because they believe the best performance status patients need to be treated with FOLFIRINOX.
TARGETED ONCOLOGY: What is important to know about toxicity management and dosing?
Kim:With paclitaxel toxicities, you hold the paclitaxel for up to a month, and about 40% of patients will go back on treatment. That's one approach. Certainly, with low white counts, neutropenia, and thrombocytopenia, you can either shorten the treatment from a 28-day cycle to a 21-day cycle, and skip day 15, or implement the break earlier. Instead of 3 treatments every month, you give them 2 treatments every 3 weeks. If you do the math, over an 8- to 9-week period, you still get 6 treatments in. Those are some of the ways you can modify the schedule. You can lower the dose. I typically would lower the gemcitabine, because that causes low platelets and low white counts. The paclitaxel carries the weight in terms of the effectiveness.
TARGETED ONCOLOGY: Can you discuss supportive care for patients with metastatic pancreatic cancer?
Kim:This is a reminder for doctors that they need to keep the supportive carethe pain control, intestinal obstruction, biliary obstruction, diabetes, blood clots—you have to keep that going, because if you don't, then it's less likely the patient will go on to what you call second-line treatment. There is data to support that patients that maintain their performance status have the opportunity to go on second-line treatment, and that's important when we start thinking about drugs in the second-line setting.
A CT scan showed response with no residual liver metastases; the tumor in the head of the pancreas remained unchanged in size. The patient was symptomatic and continued to tolerate therapy.
The patient was hospitalized for progressive pain, decreased appetite, and worsening performance status. CT showed recurrence of several liver metastases. The patient was started on the FOLFIRINOX regimen.
TARGETED ONCOLOGY: What is the trigger to change to the next line of therapy for a patient with progressive disease?
Kim:The conventional answer is that the tumors are growing. I would not really change treatments if they had stable disease. If they are developing neuropathy, then you have to change the treatment anyway.
TARGETED ONCOLOGY: Do you agree with the decision to switch to FOLFIRINOX?
Kim:If you had given that patient some radiation, they may have had less pain. The patient is hospitalized for pain, which is very common, but had you thought about radiation, maybe you could have avoided that. You don't want to eat when you're in pain, pain medications themselves suppress your appetite, so obviously if you're not eating, you're getting weaker; you're not drinking fluids.
The scan shows recurrence, and then the patient is started on FOLFIRINOX. That is not very practical. It's very hard to go from FOLFIRINOX to paclitaxel or paclitaxel to FOLFIRINOX because of the neuropathy. It's certainly something that is going to stir up a lot of discussion. But in today's world, you really want to be giving nanoliposomal irinotecan [Onivyde]. It was approved in October 2015 by the FDA showing survival advantage in patients that are refractory to gemcitabine. This patient would be better off being treated with irinotecan and 5-fluorouracil. That regimen does not have any neuropathy and does not cause low platelets or myelosuppression. It does cause neutropenia, but not low platelets. That's why more and more you're going to see patients treated with this. There were a handful of patients in the original nab-paclitaxel/gemcitabine trial that went on to FOLFIRINOX, but it was only 19 patients. It's a very small number of patients that can go from nab-paclitaxel/gemcitabine to second-line FOLFIRINOX.
TARGETED ONCOLOGY: What is your personal approach to treating patients through multiple lines of therapy?
Kim:I think gemcitabine/nab-paclitaxel is a very reasonable option upfront, and then follow it with the irinotecan regimen second-line. You want to constantly be assessing the patient, making sure that their performance status is optimized.
TARGETED ONCOLOGY: What are the options for this patient if she develops slow and steady disease progression on FOLFIRINOX?
Kim:That is why using irinotecan instead of FOLFIRINOX is important. Now you can't use nanoliposomal irinotecan. FOLFIRINOX has irinotecan in it. You're not going to use regular irinotecan and then nanoliposomal irinotecan, it doesn't make any sense. So now you're limited to treatments like gemcitabine/capecitabine, maybe even gemcitabine/cisplatin, but you run out of options if you go this approach. An experimental phase I trial is appropriate here.
A 64-year-old female was diagnosed with locally advanced pancreatic adenocarcinoma and referred for consultation at a high-volume center. CT findings showed a 2.8-cm mass in the pancreatic body, invading the common hepatic, celiac, and splenic arteries, with abutment more than 180 degrees of the superior mesenteric artery, but no encasement. Staging laparoscopy showed no distant metastasis; peritoneal washing cytology showed no malignant cells.
TARGETED ONCOLOGY: If this tumor is deemed borderline resectable, what are the recommendations for treatment?
Kim:The surgeons are the ones who make this decision, surprisingly, but they asked for chemotherapy. Certainly, FOLFIRINOX has been studied, but also nab-paclitaxel/gemcitabine can be given. The response rates with the 2 regimens are the same: 31% versus 29%. What you're trying to do is shrink the tumor away from that artery, and either regimen can accomplish that.
TARGETED ONCOLOGY: What is the role of neoadjuvant radiotherapy in locally advanced pancreatic cancer?
Kim:What I normally do is treat a patient for 2 months, do scans, and see whether the tumor is shrinking. If the tumor is not responding, many times people will switch to the other chemotherapy. For example, if you start with FOLFIRINOX and it's not responding, they will give them gemcitabine/nab-paclitaxel, and then treat for another 2 months.
I'm a fan of adding radiation. Radiation gives 30% response rates. We only fashion 28-day radiation, which takes 5.5 weeks. The alternative is stereotactic body radiation therapy. That can be given over 5 days and shortens the treatment period. It's higher doses of radiation over 5 days. That's something else that can be used, and that way you don't waste a lot of time. A month and a half of radiation is a long time.
TARGETED ONCOLOGY: Would you give chemotherapy alone or chemotherapy with radiation?
Kim:I probably would give chemotherapy, and then if that doesn't work, give them radiation with chemotherapy.
She received FOLFIRINOX followed by capecitabine and concurrent radiotherapy. Several months later, the tumor shrunk to 1.2 cm. Superior mesenteric artery encasement was diminished, but still detectable. She underwent a pancreatectomy and celiac artery resection; R0 resection. Histopathology showed fibrous changes around the celiac artery; Evans grade IIb. No evidence of residual tumor at periphery.
TARGETED ONCOLOGY: Should the patient receive adjuvant chemotherapy? If so, which regimen would you choose?
Kim:It depends on what they were treated with. If they were treated with FOLFIRINOX, then I would give them more FOLFIRINOX. I want to give a total of 6 months of treatment. Presumably, she got 6 weeks of radiation, so that counts as 2 months. So you owe her 4 months of chemotherapy. If the patient did not do well with the FOLFIRINOX or the FOLFIRINOX didn't work, then I would go with the gemcitabine/nab-paclitaxel.