Edgardo S. Santos, MD, FACP, clinical affiliate associate professor, Charles E. Schmidt College of Medicine, Florida Atlantic University, founding partner, Florida Precision Oncology, discusses the current treatment landscape for patients with squamous cell carcinoma of the lung.

Squamous cell carcinoma is a very aggressive disease in lung cancer that is typically associated with heavy smoking, Santos begins. Typically, patients with squamous cell carcinoma has a more morbid condition, since this disease is generally central in the lung. Given the location of squamous cell carcinoma, the management of this disease can be more difficult, Santos expands.

Currently, the treatment landscape of squamous cell carcinoma is focused on immunotherapy, which can be administered as monotherapy or in combination with chemotherapy, Santos notes. When a patient experiences disease progression following an immunotherapy-based regimen, either alone or in combination with chemotherapy, second-line treatment options are not as well defined, Santos expands.

In the second-line setting, clinical trials are still ongoing to attempt to identify optimal treatment strategies, Santos continues. Therapies currently recommended by the FDA in the second-line setting include gemcitabine or docetaxel alone, or docetaxel plus ramucirumab (Cyramza), Santos says. Notably, the combination of docetaxel plus ramucirumab previously demonstrated superiority to docetaxel alone in the phase 3 REVEL trial (NCT01168973) in patients with second-line non–small cell lung cancer, Santos concludes.

Videos

Edgardo S. Santos, MD, FACP, discusses the current treatment landscape for patients with squamous cell carcinoma of the lung.

Dr. Santos on the Current Treatment Landscape in Squamous Cell Carcinoma of the Lung

 Dr Santos, could you give us an overview of the NCCN [National Comprehensive Cancer Network] recommendations regarding the management of myelosuppression?

 From the NCCN, we have a stratification based on the regimen therapies for SCLC. Certain regimens carry a higher risk to developing this problem of suppression. As you mentioned, Martin, there’s the issue of not only neutropenia but also severe anemia and thrombocytopenia. There are different regimens. The NCCN recommends the use of prophylaxis on regimens that have a high risk of developing myelosuppression, which is more than 20%. There’s another category of regimen if the risk of developing myelosuppression is 10% to 20%, plus another clinical risk factors: age, bone marrow infiltration, prior radiation therapy, prior chemotherapy, and comorbidities such as diabetes, chronic obstructive pulmonary disease, and liver disease all play an important role in deciding what patient population deserves prophylactic management to avoid this myelosuppression.

 Has that changed for you in the pandemic?

 That changed significantly during the pandemic. With all the issues we’ve had in the last 2 years to avoid exposure with the patient, for obvious reason, we sometimes have had to modify not only the regimen but also our approach to being more proactive with the prophylaxis. We don’t want to send the patient¾in the middle of pandemic¾to the hospital when the health care system was completely overwhelmed with so many cases of COVID-19.

 In your clinic, if you have an extensive-stage small cell lung cancer patient, do you favor a prophylactic approach of treatment? How do you manage those patients?

 You and I are thoracic oncology. We see a lot of patients with extensive-disease small-cell lung cancer. That regimen for extensive-disease small cell lung cancer is very myelosuppressive, so we always use prophylactic treatment. In my clinic, I always use prophylactic to avoid that kind of problem. Usually, it’s neutropenia, but sometimes patients that develop pancytopenia, in which red blood cell, platelet, and white blood cell counts are depleting.

 It’s very difficult to predict what a patient is going to have.

 It’s very difficult. Some patients respond very well to prophylaxis, and some of them do not, but we’ve made progress in this field.

 Are there any unmet needs that you see for patients?

 In terms of prophylaxis, an unmet need is to continue making progress in what we have right now. We have a medication that can protect stem cells. We’re using it now, specifically in small cell lung cancer. I’d like to see an expansion in these prophylaxes¾which are proactive, not reactive¾in order to create a regimen other than 1 for a small cell lung cancer. There’s an unmet need in oncology on how to take advantage of this kind of prophylaxis and put it in another clinical setting.

Expert panelists review considerations in the prophylactic treatment of chemotherapy-induced myelosuppression with special attention paid to unmet needs related to the use of G-CSF and ESAs.

Prophylactic Approaches to the Management of CIM in ES-SCLC 

 Hello. I’m Dr Martin Dietrich from Florida Cancer Specialists & Research Institute in Orlando Florida.

 My name is Dr Edgardo Santos from Florida Precision Oncology and GenesisCare in Aventura Florida. I’m a medical oncologist. Martin, it’s nice to see you.

Thank you. We’re here during ASCO [American Society of Clinical Oncology Annual Meeting] with so many data in oncology. Let me ask you this question about chemotherapy-induced myelosuppression: how frequent is this problem in extensive-disease small cell lung cancer?

 Myelosuppression is 1 of the biggest problems and biggest needs for supportive care in small cell lung cancer. We’re seeing neutropenia in the rates of 70% or 80%. Both of us practice in Florida, in a geriatric population, so it’s almost a ubiquitous problem affecting both white and red cell lineages.

 Martin, are there any risk factors that predispose the patient to developing chemotherapy-induced myelosuppression? What do you think about those important risk factors while seeing a patient in your clinic?

 Several risk factors are present. Obviously, 1 is age. We’re seeing predisposition there. Bone marrow infiltration, if present, will probably be less frequent in small cell lung cancer. We can think about pretreatment. There are other bone marrow conditions that may be preexistent in an older-patient population: kidney dysfunction, EPO [erythropoietin] deficiency, and others. There are many predisposing factors in a real-world population that would enhance the concern of myelosuppression.

 In oncology, we have several treatments for patients with cancer. We’re going to discuss more about the treatments for extensive-stage small-cell lung cancer. What kind of therapy comes to mind when you know that you need to be more proactive because you already foresee the possibility of chemotherapy in myelosuppression? What therapy regimens come to mind right away?

 Typically, the doublets are at the top of our minds when we treat extensive-stage small cell lung cancer. Any of the regimens are aggressive and extensive, typically given over several days. Carboplatin or cisplatin have slightly different involvements with the bone marrow, but we typically see significant myelosuppression regardless. Etoposide [Toposar] and topotecan [Hycamtin] are very suppressive regimens that require growth factor supports, frequently and are oftentimes prophylactic, with an anticipated risk far above 20%¾more in the range of 80%. We’re seeing these parts. They have mostly predisposed patients to a concern of infection, hospitalization, possible sepsis, and worse outcomes. On the other hand, they’ve also affected quality of life with a significant amount of anemia, need for transfusions, low energy, shortness of breath, and the presence of preexisting conditions¾which are already prevalent in the small cell population¾ that will be aggravated by additional suppression of the bone marrow and anemia.

Dr Santos, in your patient population, what impact do you see of myelosuppression on your patients? How does it affect your treatments? How does it affect your patients in general?

 When the patient is exposed to a myelosuppressive regimen, and they develop neutropenia, there’s a serious consideration. You can develop neutropenia grade 1 or 2, no problem, but when the patient starts to get grade 3 with some symptoms or grade 4, especially with a fever, that’s an emergency situation. The patient needs to be admitted to the hospital. If the patient doesn’t have an infection, the patient can easily get back to the regimen. The patient could develop a serious infection that could become fatal, an outcome that we don’t want, or the infection will certainly cause a delay on therapy. If there’s no way to prevent that, then we have to reduce the dose sometimes. As you know, Martin, when we do dose reduction in therapy, we lose efficacy¾ several clinical trials have shown that. Dose reduction is something we prefer to avoid unless it’s extremely necessary. Certainly, the issue of neutropenia will bring a serious issue for the patient in several aspects.

 One of the most frequent emergencies that we see in medical oncology is the patient that comes into the hospital with neutropenic fever, with all the downstream effects happening.

Two leaders in the management of ES-SCLC provide an overview of chemotherapy-induced myelosuppression including key risk factors and its effect on patient outcomes.

An Overview of Chemotherapy-Induced Myelosuppression in ES-SCLC

Edgardo S. Santos, MD, clinical affiliate associate professor, Charles E. Schmidt College of Medicine, Florida Atlantic University, founding partner, Florida Precision Oncology, discusses the potential role for CEACAM5- and KEAP1-targeted therapies in non–small cell lung cancer (NSCLC).

CEACAM5 and KEAP1 are novel pathways under evaluation in NSCLC, says Santos. Targeted therapies directed toward these pathways have the potential to further evolve the treatment paradigm for this patient population. 

Moreover, therapies targeting CEACAM5 and KEAP1 could offer potential strategies for patients with NSCLC who progress on chemotherapy or chemotherapy in combination with immunotherapy, Santos explains. The frontline setting for NSCLC is currently crowded with available options, but rescue options for patients who progress after frontline treatment are more limited, Santos concludes. 

Edgardo S. Santos, MD, discusses the potential role for CEACAM5- and KEAP1-targeted therapies in non–small cell lung cancer.



Dr. Santos on the Potential Role for CEACAM5- and KEAP1-Targeted Therapies in NSCLC 

Edgardo S. Santos, MD, medical oncology, internal medicine, Boca Raton Regional Hospital, discusses exciting advancements in the field of lung cancer. Santos shared this insight during the 2016 

 State of the Science Summit on Lung Cancer.

The landscape of the treatment of lung cancer has completely changed in the last 2 weeks with the frontline approval of pembrolizumab (Keytruda) for patients who have more than 50% of PD-L1 expression on their tumor cells. That FDA approval, Santos says, recognizes the superiority of the immune checkpoint inhibitor versus standard chemotherapy for patients with adenocarcinoma as well as squamous cell carcinoma.

The approval is based on data from the phase III KEYNOTE-024 trial, in which single-agent pembrolizumab reduced the risk of death by 40% and improved progression-free survival by 4.3 months compared with doublet chemotherapy for untreated patients with advanced NSCLC with PD-L1 expression on ≥50% of cells.

When he is treating stage IV patients in the clinic, it is very gratifying for Santos to be able to discuss targeted therapy, chemotherapy, and immunotherapy. Reflecting on the current state of the science, Santos says researchers have been able to expand options for patients with treatments that have good efficacy findings and low toxicity profiles.

Edgardo S. Santos, MD, medical oncology, internal medicine, Boca Raton Regional Hospital, discusses exciting advancements in the field of lung cancer. Santos shared this insight during the 2016 OncLive State of the Science Summit on Lung Cancer.

Edgardo S. Santos, MD

Articles

Dr. Santos on the Current Treatment Landscape in Squamous Cell Carcinoma of the Lung

Prophylactic Approaches to the Management of CIM in ES-SCLC

An Overview of Chemotherapy-Induced Myelosuppression in ES-SCLC

Dr. Santos on the Potential Role for CEACAM5- and KEAP1-Targeted Therapies in NSCLC

Dr. Santos on Exciting Advancements in Field of Lung Cancer