Approaches and Obstacles to Frontline Treatment for Small Cell Lung Cancer

Melissa L. Johnson, MD (Moderator)

Program Director of Lung Cancer Research

Sarah Cannon Cancer Institute

Nashville, Tennessee

CASE SUMMARY:

A 73-year–old woman presented with shortness of breath, productive cough, chest pain, fatigue, anorexia, and recent 18-lb weight loss. She had a history of hypertension and was a 45 pack-a-year smoker. An examination showed she had dullness to percussion and decreased breath sounds.

A chest x-ray showed a left hilar mass and a 5.4 cm left upper lobe mass. A chest/abdomen/pelvis CT scan showed a hilar mass with bilateral mediastinal extension and was negative for distant metastatic disease. PET scan showed activity in the left upper lobe mass and supraclavicular nodal areas and liver lesions. An MRI showed one small asymptomatic brain lesion. An interventional radiology biopsy of the liver led to a diagnosis of small cell lung cancer (SCLC) and the patient’s ECOG performance score was 1.

DISCUSSION QUESTIONS:

• What additional workup, if any, would you order to inform your treatment recommendation?

MELISSA L. JOHNSON, MD: Is there any other workup that you would recommend before you start therapy?

MICHEL E. KUZUR, MD: I am wondering if molecular testing has any benefit here?

JOHNSON: Well, because this is a SCLC patient, I do think about molecular profiling, but I would not wait to get that result back to start therapy.

Because we know that this patient’s diagnosis is SCLC based on the liver, and that she had CT scans of the head and an MRI, and because we do not check PD-L1 status in SCLC, I would say our workup is complete, and I think we are ready to start therapy.

JOHNSON: Most of the participants responded that the majority of your patients with SCLC are not started in the inpatient setting, which is good, so they should all be treated in a frontline trial.

DISCUSSION QUESTIONS:

• What would be your approach toward treating this patient at this point, and how would you counsel them? What factors influence your recommendation?

JOHNSON: I often ask sponsors if they could let me give 1 cycle in the hospital because sometimes SCLC is a rapid diagnosis, especially with virulent symptoms, so you do not have time to wait to get them to the clinic to give chemotherapy. And so if there is 1 kind of chemotherapy I know how to give in the hospital, it is carboplatin/etoposide. Does anyone disagree?

JEFFREY FRIEDMAN, MD, PHD: I agree, but I think that for a lot of us in sort of peripheral clinics like where I practice, the issue is that it is somewhere in between needing inpatient chemotherapy and can I wait 4 weeks to get their tissue sampled for whatever it takes to get them on trial? Typically, even though I am not treating them in the hospital, I am not waiting weeks. They are getting started on treatment in a few days or else things are just going to completely go off the rails, and so I think that is the bigger hurdle when it comes to trial accrual. Even just the ancillary imaging that might be needed for a trial is just not doable.

GREGG C. SHEPARD, MD: The other issue is that probably 90% or more of patients I meet are treated for the first cycle in the hospital but then they are discharged and sent to Dr Friedman at a peripheral clinic, so he can give them a second cycle as an outpatient. So he may be choosing 90%. He treats people in the outpatient setting, but I am treating them for their first cycle usually inpatient at Ascension Saint Thomas Hospital.

JOHNSON: If you have a couple more days, and you are waiting for Dr Shepard to refer a patient to come see you, for example, or you have seen a patient at TriStar Southern Hills Hospital and you have asked them to come to clinic, what is your approach to selecting treatment? What is the algorithm that you go through when you are thinking about a new SCLC diagnosis?

JACK W. ERTER, MD: I mean, I think luckily in this disease, for better or for worse, it is not like there are 17 different options I am weighing the pros and cons of and saying, "Are they are going to be a candidate for up-front EGFR-targeted therapy or similar." I mean, this carboplatin/etoposide chemotherapy plus immunotherapy. That is what they are starting on, unless they have 4 brain metastases, in which case they need radiation treatment first.

NANCY W. PEACOCK, MD: The other thing I think is, a lot of these people that have SCLC that lands them in the hospital; they do not have a ton of psychosocial support. They delayed coming in until they got very sick because they did not have the wherewithal to get there. They do not have the support at home. They come in from the hinterlands and often the first conversation we have with them is, "This is really a very difficult diagnosis. I can give you treatment." Even if their ECOG performance status is 3, it might not be worth treating them. Everybody says, "Oh, SCLC responds," but SCLC with a poor performance status does not respond very well. I think as we are being held more and more accountable for this oncology as a cure model, trying to keep expenses down and people out of the hospital is a decision that is being made more and more, but the people I see mostly are under-insured and [not receiving enough care].

JOHNSON: Those are also absolutely relevant topics for this patient population especially. I would say that carboplatin/etoposide remains the mainstay of treatment and luckily that is cheap in the inpatient setting. Obviously, the hospitalization costs more, but it is immunotherapy that adds the true cost. But that is a good point. In terms of treatment options, how are you counseling your patients?

KUZUR: In support of what Dr Peacock mentioned, sometimes the hospitalist has already convinced the patient to go on hospice, and they consult hospice and they consult me. I sometimes have to find the option and try to convince them to try some therapy. Dr Peacock is right. Some of these people are so sick you are not able to justify that you are going to get some active results with treatment.

DISCUSSION QUESTION:

• How do you decide between carboplatin and cisplatin when using an immune checkpoint inhibitor plus chemotherapy regimen for SCLC?

JOHNSON: Does anybody want to explain why you think carboplatin or why you recommend cisplatin for a SCLC patient?

RYAN M. CARR, MD: I almost always use carboplatin, but I guess one reason I would consider cisplatin is if they have some degree of myelosuppression from some other reason to begin with, and we are able to tolerate the cisplatin, then I guess I could consider that. But almost everybody gets carboplatin with me.

ERTER: Yes. I rarely would use cisplatin and I do not think there is a big advantage in extensive-stage SCLC. I might consider it in limited curative therapy.

JOHNSON: Agreed. I think that is what our entire practice would say, and so this patient [would get] concurrent atezolizumab [Tencentriq] with carboplatin/etoposide and that was based on the IMpower133 [NCT02763579] data.