Treatment Considerations: Chemotherapy + IO in ES SCLC

Panelists reflect on key points from recent studies in ES SCLC by discussing patients for whom immunotherapy may be appropriate, examining the role of adding CTLA4 inhibition to a PD-L1 inhibitor, and reviewing factors to consider when deciding between cisplatin or carboplatin.

Hossein Borghaei, DO, MS: What do you use in your clinic? How do you choose who can get immunotherapy? Is there a patient in whom you know you’re not going to offer immunotherapy to? Can you go through your working diagnosis and everything else when you see someone in the clinic?

Wade Iams, MD: Absolutely. I approach first-line therapy in patients with extensive-stage small cell lung cancer as if chemotherapy-immunotherapy is the standard of care for all of them, unless they have severe underlying autoimmune disease, which I would define as having visceral organ damage requiring more than 10 mg of systemic glucocorticoids per day for maintenance. It’s been interesting to watch in the field, particularly within thoracic medical oncology, the expansion of immunotherapy to these populations with underlying autoimmune disease. It seems like every 6 months, there’s another study demonstrating that we can safely offer immunotherapy to patients with underlying autoimmune disease with adequately close surveillance for immune-related adverse events. There’s also the compelling line of inquiry in the field regarding the improvement in tumor control in patients who develop immune-related adverse events.

More and more, we’re expanding the cohort of patients in whom we offer chemotherapy-immunotherapy. I approach atezolizumab and durvalumab as equivalent. It would be an interesting discussion among the panelists to see if there’s anything to the tail of the curve with durvalumab or any differences others feel between the 2. But for the most part, chemotherapy-immunotherapy for all patients.

Hossein Borghaei, DO, MS: Let’s talk about the tail of the curve. It’s all the discussion now. Stephen, as 1 of the authors and presenters of 1 of the studies, what do you think of the data Anne was talking about regarding the tail of the curve? Then I’m going to go around the room and ask each of you to comment on what you think the role of CTLA4 inhibition is when it comes to small cell [lung cancer].

Stephen Liu, MD: I agree with everything Anne said, but I don’t think there’s a role for CTLA4. When I look at the tail of the curve, you’re right that the tail looks better in the durvalumab-tremelimumab arm and almost catches up to the durvalumab tail. I feel like that’s because of the durvalumab, and that the only thing tremelimumab is adding there is cost and a heck of a lot of toxicity. To me, there’s no role for CTLA4 in small cell [lung cancer].

We saw in CheckMate 032 that nivolumab-ipilimumab was capable of inducing some long-term responses, but in the follow-up randomized portion of CheckMate 032, the nivolumab-ipilimumab didn’t do anything more than the nivolumab alone. There was probably a lot of selection bias in those early nivolumab-ipilimumab studies. Ipilimumab was removed from the NCCN [National Comprehensive Cancer Network] Guidelines based on that randomized trial in CASPIAN. That tremelimumab arm was disappointing and added a lot of toxicity. It almost caught up at the end, which is reassuring, but I don’t know that tremelimumab is adding much there. We’ll see if that changes with future studies. But even though the tail is what we focus on, I didn’t see a lot of difference in the durvalumab-alone tail compared with durvalumab-tremelimumab. That direct comparison wasn’t part of the formal statistical plan, but as of now, you’re going to need to convince me there’s a role for CTLA4.

Hossein Borghaei, DO, MS: Anne, do you want to comment?

Anne Chiang, MD, PhD: I agree with you. The durvalumab was clearly positive. That’s what we use now. I’m not convinced of the role of CTLA4 right now. The CheckMate-451 trial with maintenance I/O [immuno-oncology] didn’t tell us more. That being said, I do have an IIT [investigator-initiated trial] looking at ipilimumab-nivolumab in relapsed populations; especially patients who have gotten maintenance atezolizumab. There may be a signal there. In this trial, we’re doing pretreatment and on-treatment biopsies. There’s something to be said for looking at the tumor microenvironment and specifically the infiltration of T cells, so stay tuned for that. There may be a way anti-CTLA4 may help juice up the microenvironment so that we get T cells in there so we can have a response. That being said, for the general population, I don’t think there’s a role for anti-CTLA4.

Hossein Borghaei, DO, MS: Thanks, Anne. Vivek, what do you think about CTLA4? Do you think it has a role?

Vivek Subbiah, MD: I agree with Stephen. There’s a tail end, and there’s a tail end. There are no compelling data to show that CTLA4 does something. It brings added toxicity without much clinical benefit. The community especially would definitely not favor CTLA4. Good luck finding a good biomarker for the patients in whom CTLA would benefit. That would be a sub-substudy. It would be great to find a definite biomarker in a subset of the patient population who benefits, but with the data we have, I don’t see a benefit of adding a CTLA4 to this.

Hossein Borghaei, DO, MS: Wade, what’s your take on CTLA4?

Wade Iams, MD: It has no role, but I would absolutely love to see the subset of patients who are going to have prolonged benefit identified. The infiltrating lymphocytes are the way to go. There are associations with immune-related adverse events and neurological paraneoplastic syndromes in these patients, so it’s the right population to study.

Hossein Borghaei, DO, MS: There might be a biomarker there for CTLA4. We just haven’t identified it. Hopefully we can shed some light on it. Anne, what do you think of cisplatin vs carboplatin in extensive-stage small cell? Would you say there’s a huge difference when it comes to choosing cisplatin vs carboplatin?

Anne Chiang, MD, PhD: If we look at trials in the past, for the most part, carboplatin is fine. We’re talking about patients where we’re running a marathon. This is a disease that’s not curable. We want to provide our patients with the best quality of life they can achieve. That being said, for some select populations and for young patients who are very functional, I might consider cisplatin. But for the most part for extensive-stage [lung cancer], I would use carboplatin.


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