First-Line Treatment Options for ES-SCLC

EP: 1.Case Overview: A 64-Year-Old Woman With ES-SCLC

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EP: 2.First-Line Treatment Options for ES-SCLC

EP: 3.Second-Line Treatment After Maintenance Immunotherapy

EP: 4.Safety and Efficacy of Lurbinectedin in Solid Tumors

EP: 5.The ATLANTIS Study of Lurbinectedin/Doxorubicin

EP: 6.Unmet Needs and Future Directions in ES-SCLC

Jared Weiss, MD: I’d like to think about the factors that we consider in determining the best choice of treatment. In my opinion, optimal treatment of cancer in general comes at the intersection of several axes. Patient preferences and values are primary. Assuming we have a motivated patient, the next question is how fit are they? What is possible where we’re going to have more probability of benefit than harm? We’re looking largely at organ comorbidities and performance status.

When we start to get to the mid- to late 60s, I will also perform an abbreviated geriatric assessment. In patients who clearly are not very fit or are very unfit, I will consider geriatric consultation to characterize further. Narrowing in on extensive-stage small cell, I’ll note that over the last few decades, treatment really hasn’t evolved much. We had no improvements in survival until recent years, and the evolutions we’ve had have been focused on improvements in tolerability. We moved in front line from CAV [cyclophosphamide, doxorubicin, vincristine] to carboplatin-etoposide. CAV [cyclophosphamide, doxorubicin, vincristine] then became a second-line regimen. The move from CAV [cyclophosphamide, doxorubicin, vincristine] to topotecan was largely a toxicity-based improvement as well. That really changed recently with the approval of the PD-L1 inhibitors in extensive-stage small cell starting with atezolizumab. The standard of care in the United States, as well as in other nations that can afford it, is carboplatin-etoposide and a PD-L1 inhibitor. By the hazard ratio, this gives us about a 30% improvement in survival. Unfortunately, at the median it only adds about 2 months, and PFS [progression-free survival] is still only 5 months.

In my opinion, standard-of-care treatment of front line should also include the addition of trilaciclib. Trilaciclib is a short-acting CDK4/6 inhibitor that reduces myelosuppression from cytotoxic chemotherapy and improves patient-reported outcomes. The human purposes of treating a cancer like this, which cannot be cured, are extension of duration of life. More important, if we listen to our patients, preservation of quality of life matters; therefore, a quality-of-life drug matters. If our front line is going to be carboplatin-etoposide and atezolizumab, what role is there for maintenance immunotherapy?

I’ll stop and reflect that we’ve never really had a proper study to answer contribution of components of immunotherapy in our standard of care. I’m going to be more specific about what I mean. Maintenance makes a lot of sense in small cell. Think back to the days of carboplatin-etoposide; not long ago, most patients had initial and often rather deep response to treatment that is short-lived. Small cell often presents in patient far more than anything else that I treat, and we can often make patients feel better and get them out of the hospital with that first cycle of chemotherapy. The strength is that it really works; the weakness is that it doesn’t work for a long time. Maintenance makes a lot of sense. Chemotherapy maintenance has failed. More recently, we’ve had a randomized study of the addition of nivolumab or nivolumab plus ipilimumab, and it failed. Of course, as you know, what we most recently have are 2 studies that gave immunotherapy—both in the induction period and then also subsequently in the maintenance period—that have improved survival a small amount. We are left not knowing if all of the benefit of the addition of the immunotherapy is in the induction period or if you need it in the induction and maintenance period to derive maximal benefit. In the patient who has a response to 2 cycles of triplet, carboplatin, etoposide, and a PD-L1, it’s appropriate to give 2 additional cycles. In my practice, I almost always stop at 4. But in rare cases, with a patient who’s tolerating like I’m giving them nothing, who has ongoing disease diminution and is highly motivated, I’ll consider going up to 6. Whether you stop at 4 or 6, indefinite cytotoxic is inappropriate. After 4 to 6, maintenance immunotherapy remains the standard of care.

Transcript edited for clarity.

Case: A 64-Year-Old Woman with Small-Cell Lung Cancer

Initial Presentation

• A 64-year-old woman presented with a persistent cough, chest discomfort, fatigue and unintended weight loss
• PMH: osteoporosis, hysterectomy at age 60, prediabetic managed with diet and exercise
• SH: 45-pack year smoking history; drinks alcohol 1-2/month socially
• PE: Decreased breath sounds in left lung, wheezing on auscultation, axillary lymph node enlargement

Clinical Workup

• Labs: serum Na 132 mEq/L; ALT 54 IU/L; AST 58 IU/L; all others WNL
• Axillary lymph node biopsy revealed small cell carcinoma
• Chest/abdomen/pelvic CT showed a 7.2 cm mass above the diaphragm, a small contralateral lung nodule and evidence of invasion into the left side of the pericardium
• PET scan showed activity in the left lung above the diaphragm, mediastinum and small hypermetabolic activity in the surrounding area
• Contrast‐enhanced MRI of the head was negative for 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 she complained of fatigue, shortness of breath, right upper quadrant pain and back pain
• CT scan showed hematogenous metastases in the liver
• Initiated lurbinectedin 3.2 mg/m2 IV q21 days