Assessing Treatment Options for the Case-Based Patient

EP: 1.Presentation of a Patient with Small Cell Lung Cancer

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EP: 2.Assessing Treatment Options for the Case-Based Patient

EP: 3.Defining Platinum Sensitivity vs Resistance after First-Line Treatment in Small Cell Lung Cancer

EP: 4.Analyzing the Role of Topotecan and Lurbinectedin in Small Cell Lung Cancer

EP: 5.The Impact of Lurbinectedin in Small Cell Lung Cancer

EP: 6.Evaluating Current Treatment Options for Small Cell Lung Cancer

Ticiana Leal, MD: When determining the best choice of treatment for this patient, I think 1 important factor to consider is performance status. Does this patient have adequate performance status to be able to tolerate and benefit from a triplet combination, such as platinum-etoposide with an immunotherapy agent? The other important factor to consider is the clinical stability of the patient, in terms of whether this patient needs to be admitted to manage symptoms and to optimize the clinical scenario in order to receive the therapy they need.

Some of our patients present with high symptom burden, and perhaps they have organ dysfunction or SIADH [syndrome of inappropriate antidiuretic hormone] and hyponatremia that needs to be managed as an inpatient. Perhaps they have uncontrolled symptoms due to the cancer that may require admitting the patient to the hospital to optimize and manage the symptoms and then providing the inpatient chemotherapy or transitioning and providing that therapy for the frontline setting as an outpatient.

Also, organ function is very important. Does this patient have adequate CBC [complete blood count], renal, and hepatic functions? Sometimes patients present with widely metastatic disease with liver involvement, and sometimes they have elevation of their LFTs [liver function tests] and bilirubin, which may require dose modifications for the first cycle of treatment.

Obviously, it’s very important to consider the patient’s goals and wishes. If patients present with extensive-stage small cell lung cancer and they have comorbidities and an incurable cancer, it’s very important to introduce palliative care early on and have a detailed discussion about goals of care and shared decision-making so that we take into account the patient’s goals for their course of treatment.

It’s also important to consider the course of the treatment. We talked about how this patient received 4 cycles of induction therapy with carboplatin-etoposide in combination with immunotherapy followed by maintenance therapy, which in this case is monotherapy with a PD-L1 inhibitor. This patient received atezolizumab, and this is based on the data from the phase 3 trial IMpower133. There are no other regimens approved in combination in the maintenance setting. We’ll talk about the CASPIAN data, which also similarly has the combination of chemotherapy-immunotherapy with durvalumab followed by durvalumab maintenance. However, there was a study that looked at combination immunotherapy with nivolumab plus ipilimumab. We saw that the results of the CheckMate 451 study did not show a benefit of adding combination nivolumab plus ipilimumab in the maintenance setting. As of now, the frontline strategy is the combination of chemotherapy plus immunotherapy, followed by maintenance with an agent such as durvalumab or atezolizumab.

Something to think about is whether there are patients who don’t receive chemotherapy-immunotherapy in the frontline setting. Certainly, there are a few patients who may not be candidates for immunotherapy in the frontline setting. Maybe this is a patient who has a contraindication to immunotherapy. So look at comorbidities. Does this patient have a history of a transplant that immunotherapy unfortunately is contraindicated? Or do they have an uncontrolled underlying autoimmune disorder that requires immunosuppression? This is a patient who would then not be a candidate for receiving immunotherapy. Those are other patient-related factors that are certainly important to consider when making the decision to initiate therapy in the frontline setting.

Transcript edited for clarity.

Case: A 61-Year-Old Man With Small-Cell Lung Cancer

Initial Presentation

• A 61-year-old man presented with a cough, fatigue, progressive shortness of breath
• PMH: unremarkable
• SH: 25-pack year smoking history; social alcohol use
• PE: Right lower lobe wheezing on auscultation, axillary lymph node enlargement

Clinical Workup

• Labs: WNL
• Axillary lymph node biopsy revealed small cell carcinoma
• Chest/abdomen/pelvic CT showed a 7.1 cm mediastinal conglomerate mass, with invasion into the right main and lobar pulmonary arteries; 2 small left pulmonary nodules; hypermetabolic axillary lymph node
• PET scan showed large focal hypermetabolic activity in the mediastinum and small hypermetabolic activity in the surrounding area
• Contrast‐enhanced MRI of the head showed no brain metastases
• Stage IV small-cell lung cancer; ECOG PS 0

Treatment

• Initiated carboplatin + etoposide + atezolizumab for 4 cycles; followed with atezolizumab as maintenance therapy

Follow-up

• 7 months after starting treatment he complained of shortness of breath, right upper quadrant pain and back pain
• CT showed hematogenous metastases in the liver and right adrenal gland
• Initiated lurbinectedin 3.2 mg/m2 IV q21 Days