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ES04 - Multimodality Management of Small Cell and Neuroendocrine Cancers (ID 7)
- Event: WCLC 2019
- Type: Educational Session
- Track: Small Cell Lung Cancer/NET
- Presentations: 1
- Now Available
ES04.01 - Update in Systemic Treatment of SCLC (Now Available) (ID 3168)
10:30 - 12:00 | Presenting Author(s): Sumitra Thongprasert
Chemotherapy combination of cisplatin plus etoposide is the standard option for extensive stage Small Cell Lung Cancer (SCLC); though the response rate was very high, however most cases of the extensive stage recurred within one year and there was no good regimen for second line. Several chemotherapeutic agents such as topotecan, irinotecan, amrubicin or combination of cyclophosphamide, doxorubicin and vincristine (CAV) had been used as second line treatment with minimal benefit.
Within the past couple years there’re the new way of treating lung cancer especially the use of immunotherapy, which several agents had their roles in the treatment of Non-Small Cell Lung Cancer (NSCLC). The study of immunotherapy in SCLC was very slow. The use of T cell immune-checkpoint inhibitors (anti-PD1: nivolumab, pembrolizumab; anti-PD-L1: atezolizumab, durvalumab; anti-CTLA-4: ipilimumab, tremelimumab) have shown promising antitumor activity with the potential to prolong survival in SCLC patients.
Nivolumab was the first immunotherapy agent that had approved by The US Food and Drug Administration (FDA) 2018 to be the third line drug according to the outcome in CheckMate-032, which’s a multicenter, open-label trial in patients with metastatic solid tumors. This subgroup comprised 109 patients with metastatic SCLC, with disease progression after platinum-based therapy and at least one other prior line of therapy, regardless of tumor PD-L1 status. All patients received nivolumab at3 mg/kg by intravenous infusion over 60 minutes every 2 weeks. The ORR was 12% (95% CI: 6.5, 19.5). Responses were durable for 6 months or longer in 77%, 12 months or longer in 62%, and 18 months or longer in 39% of the 13 responding patients. PD-L1 tumor status did not appear to be predictive of response.
Pembrolizumab has been granted a priority review designation by the FDA for the treatment of patients with advanced small cell lung cancer (SCLC) whose disease has progressed following ≥2 prior lines of therapy. Data from the phase II KEYNOTE-158 and phase Ib KEYNOTE-028 studies, pembrolizumab at 200 mg intravenously (IV) every 3 weeks for 2 years or until disease progression, unacceptable toxicity, or study withdrawal elicited 19% and 33% overall response rates (ORRs) in patients with extensive-stage SCLC, respectively.
Atezolizumab plus carboplatin and etoposide, was approved by FDA for the first-line treatment of adult patients with extensive-stage small cell lung cancer based on the data from IMpower133 which is a randomized treatment using atezolizumab 1200 mg and carboplatin AUC 5 mg/mL/min on day 1 and etoposide 100 mg/m2 intravenously on days 1, 2 and 3 of each 21-day cycle for a maximum of 4 cycles, followed by atezolizumab 1200 mg once every 3 weeks until disease progression or unacceptable toxicity, or placebo and carboplatin AUC 5 mg/mL/min on day 1 and etoposide 100 mg/m2 intravenously on days 1, 2, and 3 of each 21-day cycle for a maximum of 4 cycles, followed by placebo once every 3 weeks until disease progression or unacceptable toxicity. Overall survival (OS) was 12.3 months for patients receiving atezolizumab with chemotherapy and 10.3 months for those receiving placebo with chemotherapy (hazard ratio 0.70; 95% CI: 0.54, 0.91; p=0.0069). Median PFS was 5.2 months (4.4, 5.6) compared with 4.3 months (4.2, 4.5) in the atezolizumab and placebo arms, respectively (HR 0.77; 0.62, 0.96; p=0.0170).
In conclusion, there are several new ways and also new agents that target the immune cell and should be able to improve the outcome and survival of SCLC.