SCLC Treatment in the Immuno-Oncology Era: Current Evidence and Unmet Needs

Abstract

Small cell lung cancer (SCLC) represents about 13%–15% of all lung cancers. It has a particularly unfavorable prognosis and in about 70% of cases occurs in the advanced stage (extended disease). Three phase III studies tested the combination of immunotherapy (atezolizumab, durvalumab with or without tremelimumab, and pembrolizumab) with double platinum chemotherapy, with practice-changing results. However, despite the high tumor mutational load and the chronic pro-inflammatory state induced by prolonged exposure to cigarette smoke, the benefit observed with immunotherapy is very modest and most patients experience disease recurrence. Unfortunately, biological, clinical, or molecular factors that can predict this risk have not yet been identified. Thanks to these clinically meaningful steps forward, SCLC is no longer considered an “orphan” disease. Innovative treatment strategies and combinations are currently under investigation to further improve the expected prognosis of patients with SCLC. Following the recent therapeutic innovations, we have reviewed the available literature data about SCLC management, with a focus on current unmet needs and potential predictive factors. In detail, the role of radiotherapy; fragile populations, such as elderly or low-performance status patients (ECOG PS 2), usually excluded from randomized studies; predictive factors of response useful to optimize and guide therapeutic choices; and new molecular targets and future combinations have been explored and revised.

Real-world eligibility for platinum doublet plus immune checkpoint inhibitors in extensive-stage small-cell lung cancer

“…It is unclear if similar survival benefits to the large phase III studies will be realized with this pragmatic approach. Similar to prior studies, in our cohort, poor PS remained a significant negative prognostic determinant, so it would be difficult to determine whether the difference in outcomes was a consequence of the PS or the alternate treatment scheme ( 7 , 11 ). A stepped approach to treatment may mitigate toxicity risks and enable appropriate patients to receive ICIs with their platinum backbone.…”

“…Importantly, it must also be recognized that patients with poor PS (≥2) are not represented in CASPIAN or IMpower133; in addition, there is an important underrepresentation of older adults. This results in uncertainty of the clinical benefit in these patients ( 11 ). Additionally, the inclusion of patients with brain metastases in ES SCLC trials is important given their high prevalence ( 20 ).…”

“…First-line treatment has been unchanged for multiple decades given the high responsiveness to first-line platinum-based chemotherapy. Current SCLC treatment is not guided by molecular profiling due to the lack of targetable mutations ( 11 ). This has led to the evaluation of ICI in the first-line setting in conjunction with platinum-based chemotherapy in multiple trials.…”

Survival of small-cell lung cancer patients after surgery: A single-center retrospective cohort study

“…However, with advances in diagnostic and surgical technologies, many researchers have begun challenging the current view of surgery in treating SCLC and have attempted to expand the surgical indications for SCLC. 5–10…”

“…4 However, with advances in diagnostic and surgical technologies, many researchers have begun challenging the current view of surgery in treating SCLC and have attempted to expand the surgical indications for SCLC. [5][6][7][8][9][10] In the present study, we explored the value of surgery in treating SCLC. We identified relevant prognostic factors in the hope of clarifying the significance of surgery in the prognosis of SCLC patients and reassessing its importance in the multi-disciplinary treatment of SCLC.…”