Second-line treatments for small cell lung cancer are effective, but the outcomes are modest, explained Tom Stinchcombe, MD, medical oncologist, Duke Cancer Institute.
Second-line treatments for small cell lung cancer are effective, but the outcomes are modest, explained Tom Stinchcombe, MD, medical oncologist, Duke Cancer Institute. As a result, it’s important to make sure a therapy is well tolerated and improves the patient’s quality of life, he said.
In an interview with The American Journal of Managed Care® (AJMC®), Stinchcombe discussed second-line treatment options, their efficacy, side effects, and costs.
AJMC: Can you describe some of the common second-line treatment options for patients with metastatic small cell lung cancer?
Stinchcombe: For the second-line options, I think one of the first questions that comes to mind, is how well did they tolerate first-line therapy? Also, what was the treatment-free interval and what is the patient’s performance status? In my practice, patients are getting a combination of chemotherapy and immunotherapy as first-line, and after 4 cycles of the platinum-based chemotherapy they continue with single-agent immunotherapy.
If it's been 6 months since the last platinum-based therapy, I generally will retreat with platinum-etoposide alone, and I generally use carboplatin. For less than 6 months—and I realize some of these cutoffs are arbitrary—I generally think about lurbinectedin or topotecan. Of the 2, I prefer lurbinectedin because the schedule is more convenient and less of burden on patients.
Then we always look for some clinical trials at our center as well. In patients who have had a treatment-free interval of less than 3 months, the prognosis can be poor, especially if they have poor performance status.
AJMC: How effective are the second-line treatments for small cell lung cancer and what is their impact on patient outcomes?
Stinchcombe: I think they're effective in terms of response rates—lurbinectedin and the other treatments around 20% to 30% in patients with a treatment-free interval of 3 or 6 months. As you get further out from the last chemotherapy treatment, the efficacy improves. This does result in a symptomatic benefit, and other patients have their disease controlled.
But, at the same time, I think the outcomes are modest. You really have to make sure that a therapy is well tolerated and really improving the patient's quality of life.
AJMC: What are the potential side effects of second-line treatment for small cell lung cancer and how are they managed?
Stinchcombe: I think the main side effects of second-line treatment of lurbinectedin are classic chemotherapy side effects such as fatigue, loss of appetite, nausea, and lowering of the blood counts, particularly the white count or the neutrophil count. Most of the time you can manage the nausea and vomiting with good premedication for prevention of chemotherapy-related nausea and vomiting. For the blood counts, we keep a close eye on those, and those can be managed by dose adjustment of the medication.
AJMC: How do costs and access to second-line treatments impact patient care and outcomes in small cell lung cancer?
Stinchcombe: Most of the time we get these treatments covered by insurance. There's not a barrier in terms of insurance coverage. Many times, we focus on drug costs, but I think this is where sometimes we forget about the cost to the patient of traveling. So, if you do a retreatment with carboplatin and etoposide, that's a 3-day treatment. If you do the topotecan, it's treatment for 5 days in a row. Then the lurbinectedin is 1 day.
AJMC: What recent trial results and drug approvals do you find most encouraging or concerning for second-line treatment for small cell lung cancer?
Stinchcombe: I think many of us saw lurbinectedin approved on the accelerated pathway. Then the phase 3 trial1 showed it was not superior to the standards of topotecan and CAV [cyclophosphamide/doxorubicin/vincristine], which is an older regimen that is more frequently used in Europe. I think all of us are waiting on additional lurbinectedin trials to get more information about the clinical benefit.
We're also looking at the tarlatamab, which is the DLL3 bispecific antibody that's shown some promising response rates. That's not approved yet, but I think most of us are anticipating it will be approved sometime within the next year. And that's a drug with a different mechanism of action that shows promising preliminary results, particularly in terms of the duration of response.
1. Aix SP, Ciulieanu TE, Navarro A, et al. Combination lurbinectedin and doxorubicin versus physician's choice of chemotherapy in patients with relapsed small-cell lung cancer (ATLANTIS): a multicentre, randomised, open-label, phase 3 trial. Lancet Respir Med. 2023;11(1):74-86. doi:10.1016/S2213-2600(22)00309-5