2021 Research Round Up: Lung Cancer, Breast Cancer, and Sarcomas

August 5, 2021
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In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s episode, 3 Cancer.Net Associate Editors discuss new research in lung cancer, breast cancer, and sarcomas presented at the 2021 ASCO Annual Meeting, held virtually June 4-8.



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In the Research Round Up series, members of the Cancer.Net Editorial Board discuss the most exciting and practice-changing research in their field and explain what it means for people with cancer. In today’s episode, 3 Cancer.Net Associate Editors discuss new research in lung cancer, breast cancer, and sarcomas presented at the 2021 ASCO Annual Meeting, held virtually June 4-8.

First, Dr. Charu Aggarwal discusses new research on targeted therapy and immunotherapy to treat non-small cell lung cancer.

Dr. Aggarwal is a medical oncologist and Leslye M. Heisler Associate Professor for Lung Cancer in the Hematology-Oncology Division at the University of Pennsylvania’s Perelman School of Medicine. She is also the Cancer.Net Associate Editor for Lung Cancer.

View Dr. Aggarwal’s disclosures at Cancer.Net.

Dr. Charu Aggarwal: Hello, I'm Dr. Charu Aggarwal. I'm a thoracic medical oncologist, and I'm here to talk to you about research that was recently presented at the 2021 ASCO Annual Meeting. I will be discussing 3 studies of interest, and I should say that I do have a relevant disclosure to share. I have served as an adviser and consultant to AstraZeneca, which produces 1 of the compounds called durvalumab, for which I will be discussing research on. So let's start off with what was the most exciting or practice-changing research in thoracic oncology presented this year. We know that lung cancer as a field is changing quite fast and, in fact, is really becoming a poster child for application of targeted therapies. At this year's ASCO Annual Meeting, we heard about sotorasib, which is a first-in-class oral therapy that selectively and irreversibly targets the previously undruggable KRAS G12C mutant protein. KRAS G12C is an oncogene, or a molecular mutation, that occurs in patients with non-small cell lung cancer and accounts for about 13% of all patients with metastatic non-squamous non-small cell lung cancer. In a clinical trial called the CodeBreaK 100 phase 2 trial, patients with metastatic non-small cell lung cancer with this particular mutation in KRAS G12C were enrolled to receive sotorasib, which was administered orally at a dose of 960 milligrams once daily. Patients could have received previous chemotherapy or immunotherapy. And what we found was that out of the 124 patients that received therapy on this single-arm clinical trial, about 37.1% of the patients had objective clinical response, meaning that their tumors shrank when assessed by radiographic imaging.

Patients on this clinical trial had a median overall survival of about 12 and a half months, and patients were [responding] noticeably, with a response as early as 6 weeks, which was the time of the first assessment. Overall, this drug is very well-tolerated and, in fact, welcome news that the FDA approved use of this therapy for second-line and beyond treatment of patients that harbor a KRAS G12C mutation. So this is immediately practice-changing, it applies to a lot of our patients, and I think will serve as a really nice, immediate next therapeutic option in the second-line setting for our patients.

The next study that I want to talk about is the updated analysis of a trial called PACIFIC. We heard a 5-year update on this clinical trial at this year's annual ASCO meeting. For patients that have locally advanced non-small cell lung cancer, the current standard of care involves using combination chemotherapy and radiation, usually with a platinum-based chemotherapy for 6 to 7 weeks, followed by 1 year of immunotherapy with a drug called durvalumab. This standard of care has been based on a clinical trial called PACIFIC, which was first released in 2017, and then updated in 2018, showing a significant advantage to the use of this agent in the consolidation setting. At this year's meeting, we saw a 5-year update of the patients that were enrolled onto this large, phase 3 clinical trial. Patients were randomized to either receive 1 year of durvalumab or placebo following concurrent chemoradiation therapy for stage III non-small cell lung cancer.

At 5 years, we saw a consistent advantage in overall survival compared to placebo for patients that received durvalumab for 1 year following their definitive chemoradiation therapy. While these results are not immediately practice-changing, these are absolutely practice-affirming because looking at these curves at the 5-year time point really enable us to deliver the confidence to our patients that administering this 1 year of immunotherapy will help and improve overall survival and really improving the chances of cure following treatment for locally advanced, metastatic non-small cell lung cancer.

The last study that I would like to discuss is a study of adjuvant immunotherapy that is using immunotherapy after surgical resection for early-stage non-small cell lung cancer. While the study is not immediately practice-changing, I think this does represent a new paradigm. Currently, the standard of care in the post-surgical setting involves chemotherapy in case of involvement of lymph nodes and/or additional radiation therapy depending on which level of lymph nodes may be involved. This study, called the IMpower010 study, asked the question if immunotherapy in this setting following surgical resection and chemotherapy could provide a benefit. They looked at about 1,200 patients that were enrolled following surgical resection and had received 4 cycles of chemotherapy. Patients were then randomized to receive 1 year of immunotherapy with atezolizumab or best supportive care and were followed for survival.

At this year's meeting, we heard that patients who received atezolizumab, especially those patients that had stage II or IIIA non-small cell lung cancer, had a reduced chance of recurrence. Following the use of 1 year of atezolizumab, the chances of reduction in recurrence were about 34%, indicating that this is a positive study. I should add that atezolizumab for this indication has not been currently approved. Therefore, it is not practice-changing. However, I should also add that this is the first study of its kind to show an improvement in recurrence outcomes with the use of immunotherapy in the early-stage non-small cell lung cancer setting, making it a very notable study for this subgroup of patients.

Again, I think this has been a very exciting year for lung cancer research. And that wraps up our brief summary of new research in thoracic oncology from the 2021 ASCO Annual Meeting. Thank you for listening.

ASCO: Next, Dr. Norah Lynn Henry discusses two studies looking at new treatment options for early-stage breast cancer.

Dr. Henry is an Associate Professor in the University of Michigan's Division of Hematology/Oncology in the Department of Internal Medicine and is the Breast Oncology Disease Lead at the Rogel Cancer Center. She is also the Cancer.Net Associate Editor for Breast Cancer.

View Dr. Henry’s disclosures at Cancer.Net.

Dr. Norah Lynn Henry: Hi, I'm Dr. Lynn Henry, a breast cancer oncologist from the University of Michigan Rogel Cancer Center. Welcome to this quick summary of updates in breast cancer from the 2021 Virtual ASCO Annual Meeting. I have no conflicts of interest for any of the trials that I will talk about. Today I'm going to focus primarily on treatment of non-metastatic breast cancer, especially that occurs in patients who have inherited mutations in BRCA1 or BRCA2. When these 2 genes have mutations or changes that decrease their function, it increases the risk of someone developing breast cancer as well as other cancers. But it also can give us clues as to which types of treatments these cancers may respond to. I'm also going to talk about a second study that was smaller, that looked at whether allowing patients to keep their ovarian function after chemotherapy is actually a safe thing to do.

One of the biggest stories from at the ASCO Annual Meeting was the results of the OlympiA trial. So in this trial, researchers studied a type of medication known as a PARP inhibitor, which is known to be effective for treating patients with metastatic breast cancer who have inherited mutations in those 2 genes I mentioned, BRCA1 and BRCA2. However, it was not known whether giving PARP inhibitors to patients with non-metastatic breast cancer would actually decrease the likelihood of their cancer returning. Therefore, in the OlympiA trial, researchers tried to answer this question. The OlympiA trial enrolled almost 2,000 patients who had inherited mutations in either BRCA1 or BRCA2. These patients had been diagnosed with either estrogen-positive or negative breast cancer, but HER2-negative breast cancer and were at high risk of having their cancer return. In this trial, patients were randomized like the flip of a coin to treatment with either the PARP inhibitor called olaparib or to a placebo for 1 year. Patients took the study medication in addition to their usual treatments. They had mostly all had chemotherapy already, and they took it at the same time as their anti-hormone therapy. After following patients for 3 years, the researchers found that the patients who got olaparib had more than a 40% decrease in the likelihood of their cancer coming back compared to those who got the placebo. The medication was pretty well tolerated. There was some nausea and vomiting, fatigue, and lowered blood counts, although there were some rare but serious side effects that can occur. So there are some concerns about using the medicine in everybody. The follow-up of the patients has been fairly short so far, only 3 years. So it is not yet known whether taking this medicine will enable patients to live longer after breast cancer. This is a medication that has already been approved by the FDA for treatment of patients with metastatic disease. And based on these data from the OlympiA trial, ASCO guidelines now recommend that olaparib should be considered as part of treatment for patients who have either a BRCA1 or a BRCA2 mutation and who have early-stage breast cancer who are at high risk of having their breast cancer recurrence.

So to switch gears a little bit, I'll talk about the other study I also found interesting. Often very young women who are diagnosed with breast cancer would like to become pregnant after they undergo treatment with chemotherapy. For these patients who want to become pregnant in the future, we often treat them with a medicine to block the function of their ovaries during chemo, sort of to put them to sleep with the hope that it will increase the likelihood that their ovaries will wake up and resume functioning again after chemotherapy is complete. However, we have worried that preserving the function of the ovaries might increase the risk of breast cancer returning, especially for women who have hormone receptor-positive breast cancer. This is because ovaries make estrogen, which is important for those types of cancers to survive. Investigators from Italy conducted a randomized study called PROMISE-GIM6 in which patients were treated either with standard chemotherapy or they got standard chemotherapy plus the ovary-blocking medicine. Now that they followed women on this study for more than 12 years after their diagnosis of breast cancer, they presented their final results. Importantly, they found there was no difference in the likelihood of cancer returning or in survival for patients who did or did not have their ovary function blocked during chemo. So these results should be very reassuring for patients who want to try to preserve their ovary function while they're getting treatment for their breast cancer.

Now, there were a lot of other research findings presented that were related to treatment for breast cancer at the meeting. Importantly, we got glimpses of the many new drugs on the horizon for treatment of breast cancer. And we eagerly await the results of large, randomized trials so that the drugs that work can be used to care for patients with breast cancer. But for now, that's it for this quick summary of important research from the 2021 Virtual ASCO Annual Meeting. Overall, we continue on a fast track with breast cancer with many new and exciting therapies being actively studied, as well as research helping support our patients to do better than ever before. Stay tuned to Cancer.Net for future updates from upcoming breast cancer conferences.

ASCO: Thank you Dr. Henry.

Finally, Dr. Vicki Keedy discusses two studies in metastatic synovial sarcoma.

Dr. Keedy is an Associate Professor of Medicine in the Division of Hematology/Oncology and the Clinical Director of the Sarcoma Program at the Vanderbilt-Ingram Cancer Center at Vanderbilt University Medical Center. She is also the Cancer.Net Associate Editor for Sarcoma.

View Dr. Keedy’s disclosures at Cancer.Net.

Dr. Vicki Keedy: Hello, my name is Vicki Keedy, and I'm a medical oncologist at Vanderbilt University Medical Center, and I specialize in the treatment of patients with sarcomas. Today, I'm going to talk about 2 important studies discussed at the 2021 ASCO Annual Meeting. The first is the SPEARHEAD-1 trial, which is a phase 2 trial for patients with metastatic synovial sarcoma or myxoid/round cell liposarcoma. I'd like to note that my institution participated in and enrolled patients onto this trial, and I have participated as an advisor to this trial. The study evaluated an immunotherapy-based treatment called afami-cel, which targets the MAGE-A4 protein. This protein, also called an antigen, is commonly found in synovial sarcoma and myxoid/round cell liposarcoma cells. Afami-cel is called a T-cell receptor therapy, or a form of cellular immunotherapy. This therapy uses a patient's own immune cells called T cells and engineers them to be able to recognize and eliminate cells that express the MAGE-A4 protein. For this trial, patients could be between 16 and 75 years old but must have had 1 prior anthracycline, such as doxorubicin or ifosfamide-based chemotherapy. For this therapy to be effective, patients' cells must also have a specific group of markers called HLA-A02. HLA-A02 testing is performed on the patient's blood sample, while MAGE-A4 is tested on the patient's tumor tissue. Patients who are eligible for this treatment have their T cells collected through a blood draw called leukapheresis. Patients then receive a short course of chemotherapy, followed by infusion of the T cells. Patients receive no further chemotherapy unless the cancer were to progress. The majority of patients on this trial have synovial sarcoma.

The results show that 39% of patients had a partial response, meaning a decrease in tumor size by more than a third, and 2 patients had a complete response. While the number of responses is exciting, what is most exciting about these data is that these responses seem to last a long time despite the patients not receiving any further treatment for their cancer. Common side effects occurred to the chemotherapy portion of the regimen and were similar to what we would expect for chemotherapy. However, 1 particular side effect of interest for cellular therapies is called cytokine release syndrome. This occurs when inflammation occurs in response to the T-cell infusion. Patients can experience fever and flu-like symptoms or more serious illness. In this trial, 59% of patients experienced cytokine release syndrome, but only 1 patient had a more serious or grade-3 reaction. Patients must be re-monitored closely in the days and weeks following their infusion and are often hospitalized for part of this monitoring. A downside to this technology is that it requires both the correct HLA typing as well as tumor MAGE-A4 expression. In this trial population, only about 1 out of 3 patients were potentially eligible based on these 2 requirements. Having said that, the results of this trial suggest that T-cell receptor therapy against MAGE-A4 expressing synovial sarcoma and myxoid/round cell liposarcomas is a very exciting advancement for patients who are eligible for this type of treatment. Currently, this treatment is only available within a clinical trial, as it is not yet FDA approved.

Another important study reported this year were the results of catequentinib compared to dacarbazine in patients with metastatic synovial sarcoma. My institution also participated and enrolled patients on the study. Catequentinib is an oral therapy called a tyrosine kinase inhibitor. It blocks the signaling of multiple receptors that are responsible for tumor cell growth and invasion. Dacarbazine is a cytotoxic chemotherapy that is commonly used to treat patients with several types of sarcomas. To be eligible for this trial, patients must have had at least 1 prior anthracycline-containing regimen. Patients could've had a prior tyrosine kinase inhibitor, such as pazopanib, which is currently FDA approved for most sarcomas in the United States. This trial met its main endpoint of improving progression-free survival or, in other words, slowing down tumor growth, compared to dacarbazine. Although the improvement was relatively small, from 1.6 months with dacarbazine to 2.9 months with catequentinib, the data showed that there are a portion of patients who experience much longer benefit with nearly a quarter of patients still having stable disease at 1 year on the drug compared to 4% with dacarbazine. Side effects were as expected with this class of drugs, including diarrhea, fatigue, elevated liver enzymes, and high blood pressure. Catequentinib is not yet approved for use outside a clinical trial. And it is not known whether it is superior or equivalent to pazopanib, which is FDA approved for non-liposarcoma sarcomas.

These are only 2 examples of the interesting and important research being done to improve the treatment of patients with sarcoma. And while both happened to include patients with synovial sarcoma, the class of cancers known as sarcoma are actually 50 to 100 different cancers. Although it will not be possible to have a trial for every sarcoma subtype, through collaboration and patient education, we're able to research the individual sarcomas as the distinct entities that they are. Thus, it is important for patients with a metastatic sarcoma to go to centers that have trials for their specific disease when available. With this approach, we'll see even more advancements in the future for patients with sarcoma. Thank you very much for your time, and I hope I have more exciting findings to discuss in 2022.

ASCO: Thank you Dr. Keedy.  

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