Small-cell lung cancer (SCLC) is a notoriously aggressive disease where patients face a poor prognosis. Compared with non–small cell lung cancer, which has seen waves of new FDA approvals and improved patient outcomes in recent years, SCLC therapies are just trickling in.
But in the past year, the approval of durvalumab (Imfinzi) in combination with chemotherapy and the accelerated approval of lurbinectedin (Zepzelca), a novel chemotherapy agent approved for second-line treatment of SCLC, have added to the landscape of therapy options for patients with SCLC.1,2
For an overview of the SCLC armamentarium and the considerations that go into treating the disease, The American Journal of Managed Care® (AJMC®) spoke with Mary J. Fidler, MD, medical oncology section chief and associate professor in the Rush University Medical College Department of Internal Medicine’s division of hematology, oncology, and cell therapy. The following has been edited lightly for clarity:
AJMC®: Can you briefly discuss the current armamentarium for SCLC treatment?
Fidler: In 2020, we received more approvals for small-cell lung cancer. We now have 2 immune checkpoint inhibitors and a new chemotherapy agent that both damages cell genetic material and helps to lead to apoptosis. We still use platinum-doublet chemotherapy with platinum and etoposide as the backbone of treatment for more extensive-stage non-small cell lung cancer and limited-stage non-small cell lung cancer, where we are still adding in radiation therapy. Although with immune checkpoint inhibitors, this has improved survival somewhat for our extensive-stage patients.
Additionally, there are data now suggesting the potential benefit for consolidation radiotherapy to the chest if the disease is otherwise controlled in patients with stage IV small-cell lung cancer.We have been incorporating thoracic radiation more and more into our practice. Though data occurred in the absence of immune checkpoint inhibitors, given the poor prognosis of stage IV small-cell lung cancer, it is reasonable to discuss the addition of thoracic radiation while patients may be receiving atezolizumab or durvalumab maintenance therapy. We eagerly await safety and efficacy data from the NRG cooperative group trial investigating adding atezolizumab to chemoradiation for locally advanced disease (NCT03811002).
AJMC®: What disease and overall patient health factors go into selecting a therapy for newly diagnosed SCLC patient in your practice?
Fidler: Staging for small-cell lung cancer is now similar to that for non-small cell lung cancer, meaning the T, N, and M staging. We still approach these patients in the same fashion. When we meet a patient, we decide if the goal is to cure the patient or to control the disease.
In deciding upon particular therapies, the most frequent decision point is whether to use cisplatin or carboplatin. Many small-cell lung cancer patients are a little bit older and often have comorbidities, sometimes related to chronic tobacco use. And I’ve found it sometimes difficult to get the cisplatin treatment in to our limited-stage small-cell lung cancer patients. Given the difference in toxicity, ototoxicity, and neuropathy especially, I generally reserve cisplatin for those patients that are in a curative setting. I feel confident in this decision based on a metanalysis comparing cisplatin with carboplatin in patients with small cell lung cancer patients showing no difference in efficacy.3
There has been a concern in using immune checkpoint inhibitors for small-cell lung cancer with the threat of paraneoplastic disease. In reality, I do think that these drugs are quite safe for this patient population. However, if I have a small-cell lung cancer patient who did present with a paraneoplastic illness, I am more reluctant to use immune checkpoint inhibitors in this setting.
AJMC®: Are there any payer coverage issues to take into account in SCLC therapy selection?
Fidler: Well, lurbinectedin had a fast provisional FDA approval and now is available to both Medicare and private insurance patients and is on the NCCN [National Comprehensive Cancer Network] guidelines for those that have been previously treated with a platinum-doublet chemotherapy. Interestingly, the approval came so fast that, although it is on the NCCN guidelines and has provisional FDA approval, the drug has not yet made it on to all of the preferred provider lists with different payers. For example, Medicaid in Illinois was unwilling to pay for lurbinectedin because it wasn't yet on their preferred list of medications.
That being said, most pharmaceutical companies, especially with more expensive drugs, have patient assistance programs, and I have not yet had access limited by payer priority drug lists for my small-cell lung cancer patients.
AJMC®: In SCLC, new therapy options are emerging after years of lag behind NSCLC. Why do you think progress has been slower in this disease subset?
Fidler: Progress has been slow in small-cell lung cancer, but not for a want of effort. I think that the biotech support for this disease only recently is starting to make progress in targeting unique features of small-cell lung cancer. I am hopeful that we can find a better way for these patients to harness the immune system, so more patients can be long-term survivors. I also hope that the antibody drug conjugate area will move to make meaningful improvements with tolerable drugs for these patients.
AJMC®: Any final thoughts?
Fidler: I would say that we need to see more advocacy for our patients with small-cell lung cancer. I would love to see patients with small-cell feel well enough to have a bigger voice in lung cancer advocacy, and I hope that we can increase funds for this sub-optimally treated disease.
1. FDA approves durvalumab for extensive-stage small cell lung cancer. Food and Drug Administration. March 30, 2020. Accessed February 5, 2021. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-extensive-stage-small-cell-lung-cancer
2. FDA grants accelerated approval to lurbinectedin for metastatic small cell lung cancer. Food and Drug Administration. June 15, 2020. Accessed February 5, 2021. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-accelerated-approval-lurbinectedin-metastatic-small-cell-lung-cancer
3. Rossi A, Di Maio M, Ciodini P, et al. Carboplatin- or cisplatin-based chemotherapy in first-line treatment of small-cell lung cancer: the COCIS meta-analysis of individual patient data. J Clin. Oncol. 2012;30(14):1692-16698. doi:10.1200/JCO.2011.40.4905