Anne Chiang, MD, PhD, an associate professor at the Yale School of Medicine, as well as the chief network officer and deputy chief medical officer with Smilow Cancer Network, discusses the rationale for combining immunotherapy with chemotherapy in lung cancer.

The rationale for using a combination of immunotherapy and chemotherapy in lung cancer is important to consider, says Chiang. The cytotoxic effects of the chemotherapy can be used to reduce tumor burden, but a whole host of effects can also make an environment more conducive to the effects of immunotherapy, explains Chiang. For example, the T-cell-to-tumor-cell ratio can be improved, T-cell inhibitory substances can be reduced, and tumor barriers can be altered, such as the pressure or the vasculature, to allow for better T-cell penetration.

The signaling may attract more T cells and their ultimate effects, which can enable tumor cells to be killed in a way that allows downstream signaling; this prompts dendritic cell activation, migration, and, ultimately, presentation of antigens in the lymph nodes and tumor microenvironments. That is the rationale behind why a combination of chemotherapy and immunotherapy would be particularly effective in patients with lung cancer. For example, in the CheckMate-9LA trial, patients with non–small cell lung cancer were treated with nivolumab (Opdivo) plus ipilimumab (Yervoy) in combination with chemotherapy. The rationale for adding 2 cycles of chemotherapy is to harness the immediate cytotoxic effect, as previous trials with immune checkpoint inhibitors show that it takes time for the therapy to work, concludes Chiang.

Videos

Anne Chiang, MD, PhD, discusses the rationale for combining immunotherapy with chemotherapy in lung cancer.

Dr. Chiang on the Rationale for Chemoimmunotherapy in Lung Cancer

Howard A. “Skip” Burris, III, MD, FASCO, FACP, chief medical officer and president of Clinical Operations at Sarah Cannon Research Institute, 2019-2020 ASCO president-elect, and a 2014 Giant of Cancer Care® in Drug Development, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer (TNBC).

In the phase 3 IMpassion130 trial, investigators are examining atezolizumab (Tecentriq) in combination with paclitaxel in patients with TNBC. The biomarkers used in this study are helping the field to understand which patients might benefit from immunotherapy plus chemotherapy, says Burris.

There are now several opportunities to think about PD-L1 overexpression, tumor mutational burden, and microsatellite instability in this setting; this brings up the idea of cell death. It is known that chemotherapy works fairly well in TNBC, although adverse effects and how long the combination therapy can be administered are questions that still need to be addressed, concludes Burris. 

Howard A. “Skip” Burris, III, MD, FASCO, FACP, discusses using biomarkers to determine the benefits of immunotherapy and chemotherapy in triple-negative breast cancer.

Dr. Burris on Predictive Biomarkers for Chemoimmunotherapy in TNBC

Jennifer L. Atlas, MD, a medical oncologist specializing in lung cancer at Levine Cancer Institute, Carolinas HealthCare System/Atrium Health, discusses the rationale for using cemiplimab-rwlc (Libtayo) as a first intervention for patients with locally advanced cutaneous squamous cell carcinoma (CSCC).

 by the FDA for patients with metastatic CSCC or those with locally advanced CSCC who are ineligible for curative surgery or curative radiation, says Atlas.

The regulatory decision was based on favorable response rates with the agent in this patient population, adds Atlas. In a single-institution retrospective study, investigators examined cemiplimab as a first intervention in patients with locally advanced disease, multifocal disease, or nodal involvement. The goal was to see whether there was a way to give these patients systemic therapy to alter the course of their treatment. 

For those who had unresectable or marginally resectable disease, investigators wanted to learn whether it was possible to downgrade the surgery or radiation that they would ultimately receive if they did not achieve a complete response, adds Atlas. However, some of the patients went on to achieve a complete pathologic response with cemiplimab alone, concludes Atlas.

Jennifer L. Atlas, MD, discusses the rationale for using cemiplimab-rwlc as a first intervention for patients with locally advanced cutaneous squamous cell carcinoma.

Dr. Atlas on the Rationale for Cemiplimab in Locally Advanced CSCC

Jae Park, MD, a hematologist oncologist at Memorial Sloan Kettering Cancer Center, discusses considerations for CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia (ALL).

Several factors should be taken into account when considering CAR T-cell therapy for patients with ALL, says Park.

​Patients should be consulted early on regarding their eligibility for CAR T-cell therapy, ​Park explains. Then, optimizing bridging therapy ​is necessary to ensure patients have the best chance of deriving benefit from CAR T-cell therapy. 

Patients are encouraged to reach out regarding any questions they may have as a lot of preparation is involved ​prior to CAR T-cell administration, Park explains. 

In addition, clinical trials can be recommended to eligible patients​ as ALL remains a rare disease, Park concludes. 

Jae Park, MD, discusses considerations for CAR T-cell therapy in relapsed/refractory acute lymphoblastic leukemia.

Dr. Park on Considerations of CAR T-Cell Therapy in Relapsed/Refractory ALL 

Jonathan C. Trent, MD, PhD, professor and associate director for Clinical Research at the Sylvester Comprehensive Cancer Center, University of Miami Health System, discusses the role of circulating tumor DNA (ctDNA) in soft tissue sarcoma. 

ctDNA could ​play an important role in terms of therapy selection following imatinib (Gleevec) resistance, says Trent. 

For example, patients with secondary-resistant, 

 exon 13​–mutant gastrointestinal stromal tumors (GISTs) seem to be sensitive to sunitinib (Sutent), despite being resistant to other TKIs. 

 exon 17–mutant GIST​s who are resistant to imatinib seem to be resistant to sunitinib but sensitive to other TKIs, Trent concludes. 

Jonathan C. Trent, MD, PhD, discusses the role of circulating tumor DNA in soft tissue sarcoma. 

Dr. Trent on the Role of ctDNA in Soft Tissue Sarcoma 

Ronald Hoffman, MD, a professor of medicine, hematology, and medical oncology at Mount Sinai, discusses the design of an ongoing phase 2 trial (NCT04057040) evaluating the first-in-class synthetic hepcidin mimetic PTG-300 in patients with polycythemia vera. 

According to Hoffman, there are 3 components to the trial. The dose-finding component will determine the optimal dose of PTG-300 that can maintain a patient’s hematocrit levels below 45%, says Hoffman. 

Once the optimal dose has been established, patients will be randomized to continue on treatment with PTG-300 or placebo, Hoffman explains. The goal of this portion of the study is to determine whether erythrocytosis will return in patients who are receiving placebo. 

Finally, patients randomized to placebo will receive PTG-300 in the continuation phase of the study, Hoffman says. As the frequency of phlebotomy is a metric that is being used to determine the efficacy of PTG-300, eligible patients have to have had more than 3 phlebotomies over a period of 6 months prior to study entry, concludes Hoffman. 

Ronald Hoffman, MD, discusses the design of an ongoing phase 2 trial evaluating the first-in-class synthetic hepcidin mimetic PTG-300 in patients with polycythemia vera. 


Dr. Hoffman on the Design of an Ongoing Trial Testing PTG-300 in Polycythemia Vera 

Toni K. Choueiri, MD, director of the Lank Center for Genitourinary Oncology, director of the Kidney Cancer Center, and senior physician at Dana-Farber Cancer Institute, as well as the Jerome and Nancy Kohlberg chair and professor of medicine at Harvard Medical School, discusses the impact the coronavirus disease 2019 (COVID-19) pandemic has had on diagnosing and treating patients with renal cell carcinoma (RCC).

Even prior to COVID-19, treatment options were debated in RCC, says Choueiri.

Now, given the ongoing pandemic, even more nuanced discussions are taking place regarding the timing of therapy and surgery, Choueiri explains.

Patients with RCC often receive cytotoxic chemotherapy. Now, cytotoxic chemotherapy is commonly given in combination with growth factor support to mitigate the potential of developing neutropenic fever which could bring a patient into the hospital, says Choueiri. 

Toni K. Choueiri, MD, discusses the impact the coronavirus disease 2019 pandemic has had on diagnosing and treating patients with renal cell carcinoma.  


Dr. Choueiri on the Impact of the COVID-19 Pandemic on Treatment in RCC 

Sara A. Hurvitz, MD, associate professor at the David Geffen School of Medicine, University of California, Los Angeles (UCLA) medical director of the Jonsson Comprehensive Cancer Center Clinical Research Unit, co-director of the Santa Monica-UCLA Outpatient Oncology Practices, and director, Breast Cancer Clinical Trials Program, UCLA, discusses the lack of predictive biomarkers in HER2-positive breast cancer.

Biomarkers such as tumor-infiltrating lymphocytes, PD-L1 expression, hormone receptor (HR) co-expression, and 

 mutations have been evaluated in HER2-positive breast cancer, explains Hurvitz. 

However, no biomarkers have emerged that can determine whether a patient is likely to respond to HER2-targeted therapy, Hurvitz says.

Factors such as nodal status and HR co-expression are used to determine which therapies should be given in addition to trastuzumab, says Hurvitz. 

, biomarker analyses from the phase 3 KATHERINE study revealed that patients responded to adjuvant ado-trastuzumab emtansine (Kadcyla; T-DM1), irrespective of HR status, 

 mutational status, nodal status, or burden of residual disease at the time of surgery, Hurvitz concludes.

Sara A. Hurvitz, MD, discusses the lack of predictive biomarkers in HER2-positive breast cancer.  



Dr. Hurvitz on the Lack of Predictive Biomarkers in HER2+ Breast Cancer 

Karen Kelly, MD, associate director for Clinical Research at the University of California (UC) Davis Comprehensive Cancer Center, Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon Endowed Chair in Cancer Clinical Research, and a professor of medicine at UC Davis Health, discusses the experimental window-of-opportunity studies with monotherapies in lung cancer.

Right now, window-of-opportunity studies remain very experimental, says Kelly. Two small phase 2 trials examining monotherapy in lung cancer. A larger trial, LCM3, enrolled 180 patients with locally advanced non–small cell lung cancer who underwent treatment with atezolizumab (Tecentriq); however, the rest of the studies reported have been very small.

The field did see some evidence of major pathologic response, although this is a surrogate that needs to be validated in this setting of neoadjuvant therapy because that is the earliest time point for efficacy, explains Kelly.

The next time point would be disease-free survival and finally overall survival (OS), but the wait for OS read-outs is very long, says Kelly. Major pathologic response has been the primary end point for most of these window-of-opportunity studies, concludes Kelly.

Karen Kelly, MD, discusses the experimental window-of-opportunity studies with monotherapies in lung cancer.

Dr. Kelly on Window-of-Opportunity Monotherapy Trials in Lung Cancer

Noopur S. Raje, MD, professor of medicine at Harvard Medical School and director of the Multiple Myeloma Program at Massachusetts General Hospital, discusses recent findings with melflufen in relapsed/refractory multiple myeloma.

Melflufen is a novel alkylating agent with less toxicity, says Raje. The phase 2 HORIZON trial enrolled patients with relapsed/refractory multiple myeloma who were refractory to pomalidomide (Pomalyst) and/or an anti-CD38 monoclonal antibody. The combination of melflufen and dexamethasone was effective in patients with triple-refractory disease and the median duration of response was also significant, says Raje. 

These results underscored that in a particularly difficult population to treat, the old alkylating agent still had efficacy. The trial included many patients who already had melphalan and many had received prior high-dose chemotherapy; even so,some notable efficacy was observed. This is a good weapon to have in the treatment armamentarium, especially in the triple-refractory patient population where response rates can be dismal, concludes Raje.

Noopur S. Raje, MD, discusses recent findings with melflufen in relapsed/refractory multiple myeloma.

OncLive TV