Written by: Joshua Nubla, PharmD, NCODA
The purpose of this PQI is to discuss Stage III Non-small cell lung cancer (NSCLC) and patient eligibility.
Within the category of Lung Cancer, approximately 80% to 85% of lung cancers are NSCLC.3,5 Treatment for stage III NSCLC may include combinations of radiation, chemotherapy, and/or surgery, which requires input from the medically integrated team, including medical and radiation oncologists along with thoracic surgeons. Concurrent chemoradiation therapy (CRT) is often utilized when patients with Stage III NSCLC either decline or are ineligible for surgical options.4 Immunotherapy is possible to be given at this stage with durvalumab being the standard of care in patients who have not progressed after 2 or more cycles of definitive concurrent CRT. Meta-analysis has shown that concurrent CRT confers significant benefit when it comes to long-term survival of patients with for NSCLC (2,3,4, and 5-year survival rates).6 NCCN guidelines suggest use of durvalumab as the Category 1 recommendation in unresectable Stage III NSCLC following definitive CRT.2 Initiation of durvalumab following CRT may also elicit a synergistic antitumor immune response, given the mechanism of durvalumab as a monoclonal antibody that binds to programmed cell death ligand-1 (PD-L1), thereby blocking the PD-L1/PD-1 immune checkpoint signaling cascade.8-13 Based on the PACIFIC study criteria approximately 70% of patients with unresectable stage III NSCLC would be eligible to receive durvalumab following CRT.7 If initiating durvalumab, therapy care teams are instructed to begin therapy within 42 days after CRT completion.1
- Consider durvalumab for Non-small Cell Lung Cancer (NSCLC) if ALL of the following criteria are met:
- Individual is 18 years of age or older
- Individual has not received previous therapy with a programmed death receptor-1 (PD-1) or PD-L1 -directed therapy (ex. nivolumab, pembrolizumab, atezolizumab, avelumab, cemiplimab, etc.) unless otherwise specified
- Confirmed diagnosis of any ONE of the following:
- NSCLC if ALL of the following:
- Used as a single agent
- Used as consolidation therapy
- Disease is unresectable stage III without progression after 2 or more cycles of definitive CRT
- Individual has performance status (PS) 0-1 (World Health Organization grading)
- 0-1 performance status is when individual is able to perform all pre-disease activities without restriction or restricted when engaging in physical activity but able to carry out light work
- NSCLC if ALL of the following:
- If durvalumab is a potential option post-CRT, especially with concurrent CRT, plan to initiate durvalumab within 42 days of CRT based on clinical appropriateness and discretion
Patient Centered Activities:
- Review with patient potential options for stage III NSCLC
- For durvalumab therapy: review PQI Durvalumab (Imfinzi) Therapy Overview for management guidance
- When administering immunotherapy
- Counsel patient on immune-mediated adverse event (imAE) symptoms and when to report symptoms to oncologist
- Schedule regular visits for blood tests (CBC, renal, hepatic, pancreatic, thyroid) and monitoring
- Consider early initiation of steroids as necessary
Diagram of durvalumab’s current place in therapy for NSCLC2
- Imfinzi (durvalumab) [prescribing information]. Wilmington, DE. AstraZeneca Pharmaceuticals LP.; 2021
- NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) for Non-Small Cell Lung Cancer V.4.2021.
- American Cancer Society. https://www.cancer.org/cancer/lung-cancer/about/what-is.html. Accessed March 2021
- American Cancer Society. https://www.cancer.org/cancer/lung-cancer/treating-non-small-cell/by-stage.html. Accessed March 2021
- Chiramel J., Tay R., Califano R. Durvalumab after chemo-radiotherapy in stage III non-small cell lung cancer. J Thorac Dis. 2018;10(Suppl 9):S991–S994.
- Xiao W, Hong M. Concurrent vs sequential chemoradiotherapy for patients with advanced non-small-cell lung cancer: A meta-analysis of randomized controlled trials. Medicine (Baltimore). 2021 Mar 19;100(11):e21455.
- Sakaguchi T, Ito K, Furuhashi K, Nakamura Y, Suzuki Y, Nishii Y, Taguchi O, Hataji O. Patients with unresectable stage III non-small cell lung cancer eligible to receive consolidation therapy with durvalumab in clinical practice based on PACIFIC study criteria. Respir Investig. 2019 Sep;57(5):466-471.
- Reits EA, Hodge JW, Herberts CA, et al. Radiation modulates the peptide repertoire, enhances MHC class I expression, and induces successful antitumor immunotherapy. J Exp Med. 2006;203(5):1259-1271.
- Dovedi SJ, Adlard AL, Lipowska-Bhalla G, et al. Acquired resistance to fractionated radiotherapy can be overcome by concurrent PD-L1 blockade. Cancer Res. 2014;74(19):5458-5468.
- Deng L, Liang H, Burnette B, et al. Irradiation and anti–PD-L1 treatment synergistically promote antitumor immunity in mice. J Clin Invest. 2014;124(2):687-695.
- Stewart R, Morrow M, Hammond SA, et al. Identification and characterization of MEDI4736, an antagonistic anti–PD-L1 monoclonal antibody. Cancer Immunol Res. 2015;3(9):1052-1062.
- Hato SV, Khong A, de Vries IJ, Lesterhuis WJ. Molecular pathways: the immunogenic effects of platinum-based chemotherapeutics. Clin Cancer Res. 2014;20(11):2831-2837.
- Ibrahim R, Stewart R, Shalabi A. PD-L1 blockade for cancer treatment: MEDI4736. Semin Oncol. 2015;42(3):474-483.