A systematic literature review of real-world treatment outcomes of small cell lung cancer

Abstract

Background: Robust evidence from real-world studies is needed to aid decision-makers and other stakeholders in choosing the best treatment options for patients. The objective of this work was to assess real-world outcomes of treatment strategies for limited- and extensive-stage small cell lung cancer (SCLC) prior to the global introduction of immunotherapies for this disease.

Methods: Searches were conducted in MEDLINE and Embase to identify articles published in English from October 1, 2015, through May 20, 2020. Searches were designed using a combination of Medical Subject Heading (Medline), Emtree (Embase subject headings), and free-text terms such as SCLC. Observational studies reporting data on outcomes of initial treatment strategies in patients with limited- and extensive-stage SCLC were included. Studies with limited sample sizes (<100 patients), enrolled all patients prior to 2010, or did not report outcomes for limited- and extensive-stage SCLC separately were excluded. Data were extracted into a predesigned template by a single researcher. All extractions were validated by a second researcher, with disagreements resolved via consensus.

Results: Forty articles were included in this review. Most enrolled patients from the United States (n = 18 articles) or China (n = 12 articles). Most examined limited-stage (n = 27 articles) SCLC. All studies examined overall survival as the primary outcome. Articles investigating limited-stage SCLC reported outcomes for surgery, chemotherapy and/or radiotherapy, and adjuvant prophylactic cranial irradiation. In studies examining multiple treatment strategies, chemoradiotherapy was the most commonly utilized therapy (56%-82%), with chemotherapy used in 18% to 44% of patients. Across studies, median overall survival was generally higher for chemoradiotherapy (15-45 months) compared with chemotherapy alone (6.0-15.6 months). Studies of extensive-stage SCLC primarily reported on chemotherapy alone, consolidative thoracic radiotherapy, and radiotherapy for patients presenting with brain metastases. Overall survival was generally lower for patients receiving chemotherapy alone (median: 6.4-16.5 months; 3 years, 5%-14.9%) compared with chemotherapy in combination with consolidative thoracic radiotherapy (median: 12.1-18.0 months; 3 years, 15.0%-18.1%). Studies examining whole-brain radiotherapy for brain metastases reported lower median overall survival (5.6-8.7 months) compared with stereotactic radiosurgery (10.0-14.5 months).

Conclusions: Under current standard of care, which has remained relatively unchanged over the past few decades, prognosis remains poor for patients with SCLC.

Figure 1.

Flow diagram of study selection process. ^aCombined hits from searches described in Supplementary Tables 1 to 2, http://links.lww.com/MD/G814. ^bStudies included in the synthesis of results (studies reporting data on outcomes of initial treatment strategies). RCT = randomized controlled trial, SCLC = small cell lung cancer, SLR = systematic literature review.

Figure 2.

Use of treatment strategies for (A) limited-stage SCLC and (B) extensive-stage SCLC. *Study was limited to patients undergoing chemotherapy. Other category includes: **no chemo or radiotherapy; ^†surgery only; ^&not reported in article; ^#chemotherapy (without consolidative TRT); ^∏chemotherapy (without PCI); ^‡enrollment from single study center. Note: [xx], reference number; studies enrolling patients across multiple treatment strategies depicted in figure. CRT = chemoradiotherapy, CT = chemotherapy, PCI = prophylactic cranial irradiation, RT = radiotherapy, TRT = thoracic radiotherapy, US = United States.

Figure 3.

Median OS (months) of limited-stage SCLC nonsurgical treatment strategies. Note: [xx], reference number. BID = twice daily, CR = complete response, CRT = chemoradiotherapy, CT = chemotherapy, IST = interval of simultaneous treatment, PCI = prophylactic cranial irradiation, PET = positron emission tomography, PR = partial response, QD = daily, RT = radiotherapy.

Figure 4.

Median OS (months) of extensive-stage SCLC treatment strategies. Note: [xx], reference number. BM = brain metastases, CE = carboplatin-etoposide, CT = chemotherapy, EP = etoposide-platinum, PCI = prophylactic cranial irradiation, RT = radiotherapy, SRS = stereotactic radiosurgery, TRT = thoracic radiotherapy, WBRT = whole-brain radiotherapy.