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Research from Rutgers Cancer Institute of New Jersey shows administering the immunotherapy drug pembrolizumab together with chemotherapy given at the same time as radiation treatment (chemoradiation) is safe and tolerable as a first-line therapy for patients with stage 3 non-small cell lung cancer (NSCLC). The work, stemming from a multi-center phase 1 clinical trial led by Rutgers Cancer Institute, is published in the February 20 online edition of JAMA Oncology.

“Locally advanced NSCLC accounts for 20 to 25 percent of all new diagnoses of NSCLC, with five-year overall survival rates of between 25 to 30 percent when standard therapy is given. Current standard treatment in which an immunotherapy drug is administered after chemoradiaton offers a 57 percent progression-free survival rate compared to 43.5 percent when chemoradiation is given alone. Our team wanted to examine the safety and tolerability of the immunotherapy drug pembrolizumab when administered concurrently with chemoradiation, as we’ve learned from first-line treatment of stage 4 disease that we see better patient outcomes the earlier immunotherapy is given,” shares Rutgers Cancer Institute radiation oncologist Salma Jabbour, MD, who is the lead and corresponding author of the current work.

Typically, the human body’s immune system recognizes abnormal cells in the body and destroys them. Cancer cells frequently create proteins (PD-L1, programmed cell death ligand-1) on the cell surface that act as signals to turn off this part of the immune system. Pembrolizumab is a drug approved by the Food and Drug Administration to treat melanoma and other forms of cancer that targets PD-1 receptors, which act as a signaling ‘switch.’ Pembrolizumab blocks this action and turns the ‘switch’ back on, allowing the immune system to recognize cancer cells as foreign and attack them.

For a 27 month period between 2016 and 2018, 23 participants were enrolled (52 percent were women; median age 69 years). Five cohorts evaluating different timing and dosing of pembrolizumab combined with chemotherapy (carboplatin and paclitaxel weekly) and definitive radiation therapy (60 Gy in 2 Gy/day x 30 fractions) for unresectable, locally advanced, stage 3 disease were examined. Median follow-up time was 16 months.

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Results show the combined treatment is feasible and well tolerated with a 12-month progression-free survival of 69.7 percent. Clinical benefit accounted for 94.6 percent at a median of 12.6 months. Of 19 evaluable patients (those who received 2 or more cycles of pembrolizumab) for response, the best response to therapy was a partial response seen in 73.7 percent, followed by 15.8 percent with a complete response, and 5.3 percent with stable disease. Local progression occurred in one patient, and of the six who developed metastatic disease, the median time to metastatic disease was 14.7 months. While there was an increased rate of pneumonitis, the authors note that patients with this form of lung inflammation responded to high-dose steroid treatment.

This study demonstrates that the combination of immunotherapy with chemoradiation has the potential to improve cure rates for patients with stage 3 non-small cell lung cancer.”

Dr. Salma Jabbour, professor of radiation oncology at Rutgers Robert Wood Johnson Medical School

Given the risk of pneumonitis when pembrolizumab is given with chemoradiation, the authors note further evaluation of the treatment combination through clinical trials is warranted, where careful radiation design to limit key lung parameters and biomarkers can be implemented. They add study limitations include the small sample size and limited follow-up duration.

Source:

Rutgers Cancer Institute of New Jersey

Journal reference:

Jabbour, S.K, et al. (2020) Phase 1 Trial of Pembrolizumab Administered Concurrently With Chemoradiotherapy for Locally Advanced Non–Small Cell Lung Cancer. JAMA Oncology. doi.org/10.1001/jamaoncol.2019.6731.

Earlier this year, doctors and researchers celebrated the news that the five-year survival rate for pancreatic cancer had crossed into double digits for the first time -; up from just 6% in 2011.

And while researchers at the University of Michigan Rogel Cancer Center and elsewhere continue to pursue scientific insights into the disease and develop new therapeutic approaches, surgeons on the front line of patient care are also working hard to improve outcomes.

Hari Nathan, M.D., Ph.D., an assistant professor of surgery at Michigan Medicine, sat down with the Michigan Health blog to talk about recent advances in surgical care for patients with pancreatic cancer, and some things patients should look for when evaluating where to seek treatment.

Growing evidence that starting chemo before surgery could improve survival

The best approach for treating pancreatic cancer remains physically removing the cancer through surgery, also called resection, in combination with chemotherapy and sometimes radiation therapy, Nathan says.

"It's been known for decades that adding chemotherapy to resection for pancreas cancer improves survival," he says. "It's a very difficult disease to begin with, and the survival rates are still unacceptably low compared to the progress we have made in a variety of other cancers. But rates are improving -; and part of the reason they're improving is the development of more effective chemotherapy regimens over time."

Recently, surgeons at Michigan Medicine have adopted an emerging practice of administering some or all of a patient's chemotherapy before they undergo an operation.

One recent study, for example, found that patients who underwent chemo before surgery -; known as neoadjuvant chemotherapy -; had a two-year survival rate of 63.7% compared to 53.5% in those who received surgery first.

That difference is driven by multiple reasons. Even in the best hands, these operations are challenging and can be fraught with complications. And we know that when we give chemotherapy after an operation, roughly half of patients aren't healthy enough to complete the intended course."

Hari Nathan, M.D., Ph.D., assistant professor of surgery at Michigan Medicine

Giving chemotherapy on the front end -; before a major operation takes a toll on a patient's body -; increases the likelihood they'll complete more of their chemotherapy, which, in turn, is correlated with better outcomes, he notes.

For some patients, earlier administration of chemotherapy could spare them from going through an operation if there are signs it won't be effective.

"A small percentage of patients will develop additional disease during chemotherapy, or have progression of the tumor," Nathan says. "That's a warning sign that their disease is more aggressive and putting them through a major operation may not be helpful to them."

Helping more patients become candidates for surgery

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In addition to improving the number of patients who complete their course of chemo, the neoadjuvant approach is also expanding the number of patients who are candidates for surgery, Nathan says.

"What we often find with these newer chemotherapy regimens is that they actually can kill parts of the tumor that will make an operation more viable," he says.

In the past, a patient may have been told that their tumor wasn't resectable because it was wrapped around a vital artery.

"But if we can kill off the part of the tumor that was a barrier to a successful surgery, then it makes it possible to go in and do the operation," Nathan says.

"In a lot of ways, what we're doing in pancreatic cancer now mimics what we've been doing in other cancers for a while," he adds. "The difference is that in colorectal cancer, for example, we've had more effective chemotherapy agents, and so we've been willing to be more surgically aggressive. And now with pancreatic cancer, we're finally getting to that point where we have these more effective chemotherapy regimens."

Where patients get care can make a big difference

There are a number of reasons why receiving care at a nationally ranked hospital or academic medical center, like Michigan Medicine, can also make a big difference for patients, Nathan says.

The first is access to new, otherwise unavailable experimental treatments through clinical trials.

For example, Nathan says, U-M is a site for a trial enrolling patients who are not initially eligible for surgery because their pancreatic cancer involves major blood vessels or other tissue in the abdomen. The trial is to test an investigational medicine that helps chemotherapy to better attack the tumor, with a goal, ultimately, of making the patients candidates for surgery.

Second, larger, high-volume, multidisciplinary centers will have more experience in specifically treating pancreatic cancer (Michigan Medicine was recently designated a National Pancreas Foundation Center of Excellence for Pancreatic Cancer, one of just two in the state.)

"I would argue that medical centers like U-M, by virtue of the breadth and depth of the system as a whole, can provide the highest quality care," Nathan says. "In addition to the quality of our surgeons, our medical oncologists, radiation oncologists, radiologists, geneticists and nutritionists all have expertise in pancreatic cancer. Everybody in our multidisciplinary pancreatic clinic has a large focus of their practice devoted to taking care of patients with pancreas cancer. That's not the case everywhere."

Source:

Michigan Medicine – University of Michigan