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Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer.

Publication ,  Journal Article
Perez, BA; Kim, S; Wang, M; Karimi, AM; Powell, C; Li, J; Dilling, TJ; Chiappori, A; Latifi, K; Rose, T; Lannon, A; MacMillan, G; Saller, J ...
Published in: Int J Radiat Oncol Biol Phys
February 1, 2021

PURPOSE: Consolidative thoracic radiation therapy (TRT) has been shown to improve outcomes for patients with extensive stage small cell lung cancer. We hypothesized that the addition of ipilimumab (IPI) and nivolumab (NIVO) after TRT would improve outcomes for patients with extensive stage small cell lung cancer. METHODS AND MATERIALS: Eligibility required stable disease or better after platinum doublet chemotherapy. Study therapy included consolidative TRT to 30 Gy in 10 fractions, targeting residual primary tumor and initially involved regional lymph nodes. Two weeks after TRT, patients received concurrent IPI (3 mg/kg) and NIVO (1 mg/kg) every 3 weeks for 4 doses followed by NIVO monotherapy (480 mg) every 4 weeks until progression or up to 1 year. RESULTS: The study enrolled 21 patients, with 6-month progression-free survival (PFS) of 24% (90% confidence interval [CI], 11%-40%) and a median PFS of 4.5 months (95% CI, 2.7%-4.6%). The 12-month overall survival (OS) was 48% (95% CI, 29%-64%) with a median OS of 11.7 months (95% CI, 4.7%-16.0%). Fifty-two percent of patients had ≥1 possibly related grade 3 to 4 immune-related adverse event. Grade 3 pulmonary and gastrointestinal immune-related adverse events were recorded in 19% and 24% of patients, respectively. Exploratory analysis showed increased cytotoxic T cell (CD3+CD8+) tumor infiltration was associated with favorable PFS (P = .01) and OS (P = .02). Reduction in peripheral blood CD3+CD8+ from baseline to after first dose of IPI/NIVO was associated with improved PFS (P = .02) and OS (P = .02). CONCLUSIONS: Consolidative IPI and NIVO after platinum-based chemotherapy and TRT demonstrated a toxicity profile consistent with the known adverse events attributable to IPI and NIVO. Although the study regimen did not significantly improve PFS, the OS was higher than historic expectations. CD3+CD8+ tumor infiltration and migration may identify patients most likely to have improved outcomes in small cell lung cancer.

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Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

February 1, 2021

Volume

109

Issue

2

Start / End Page

425 / 435

Location

United States

Related Subject Headings

  • Thorax
  • Small Cell Lung Carcinoma
  • Prospective Studies
  • Progression-Free Survival
  • Platinum
  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasm Staging
  • Middle Aged
  • Male
 

Citation

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Perez, B. A., Kim, S., Wang, M., Karimi, A. M., Powell, C., Li, J., … Antonia, S. J. (2021). Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys, 109(2), 425–435. https://doi.org/10.1016/j.ijrobp.2020.09.031
Perez, Bradford A., Sungjune Kim, Minhsuan Wang, Ahmad M. Karimi, Chase Powell, Jiannong Li, Thomas J. Dilling, et al. “Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer.Int J Radiat Oncol Biol Phys 109, no. 2 (February 1, 2021): 425–35. https://doi.org/10.1016/j.ijrobp.2020.09.031.
Perez BA, Kim S, Wang M, Karimi AM, Powell C, Li J, et al. Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2021 Feb 1;109(2):425–35.
Perez, Bradford A., et al. “Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer.Int J Radiat Oncol Biol Phys, vol. 109, no. 2, Feb. 2021, pp. 425–35. Pubmed, doi:10.1016/j.ijrobp.2020.09.031.
Perez BA, Kim S, Wang M, Karimi AM, Powell C, Li J, Dilling TJ, Chiappori A, Latifi K, Rose T, Lannon A, MacMillan G, Saller J, Grass GD, Rosenberg S, Gray J, Haura E, Creelan B, Tanvetyanon T, Saltos A, Shafique M, Boyle TA, Schell MJ, Conejo-Garcia JR, Antonia SJ. Prospective Single-Arm Phase 1 and 2 Study: Ipilimumab and Nivolumab With Thoracic Radiation Therapy After Platinum Chemotherapy in Extensive-Stage Small Cell Lung Cancer. Int J Radiat Oncol Biol Phys. 2021 Feb 1;109(2):425–435.

Published In

Int J Radiat Oncol Biol Phys

DOI

EISSN

1879-355X

Publication Date

February 1, 2021

Volume

109

Issue

2

Start / End Page

425 / 435

Location

United States

Related Subject Headings

  • Thorax
  • Small Cell Lung Carcinoma
  • Prospective Studies
  • Progression-Free Survival
  • Platinum
  • Oncology & Carcinogenesis
  • Nivolumab
  • Neoplasm Staging
  • Middle Aged
  • Male