Do you incorporate immunotherapy in your multi-modality treatment after chemoradiation for patients with potentially resectable stage III superior sulcus NSCLC?
For stage III superior sulcus NSCLC, do you incorporate immunotherapy?
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No. Durvalumab therapy in NSCLC is currently limited to patients with unresectable disease. PACIFIC clearly demonstrated an enduring survival benefit of consolidative Durvalumab therapy after combined chemo-radiation therapy in patients who did not undergo surgical resection. The NeoCOAST trial is currently exploring the role of Durvalumab in the neo-adjuvant setting. Superior sulcus NSCLC is unique because the most widely accepted standard of care, based on S9416/INT-0160 (a single arm Phase II trial, now almost 20 years old) involves trimodality therapy with neoadjuvant chemoradiation followed by definitive surgical resection. The role of immune checkpoint inhibitors in the setting of trimodality therapy is unknown. No existing neoadjuvant and adjuvant therapy trials have tested the addition of immunotherapy to the combination of chemotherapy, radiation therapy, and surgery.
S1934, the ongoing randomized Phase II superior sulcus NSCLC trial, compares trimodality versus ‘quadrimodality’ (trimodality + Atezolizumab) therapy. Patients assigned to the investigational arm are scheduled to receive 4 cycles of Atezolizumab concurrently with chemotherapy and radiation therapy before surgery, and 1 year of maintenance Atezolizumab after surgery. The rationale for maintenance Atezolizumab is to explore the possibility of reducing distant (especially CNS) recurrence which continues to be the major challenge in superior sulcus NSCLC.
Patients on the standard treatment arm do not receive immunotherapy because the benefits and safety of immune checkpoint inhibitor therapy, when super-imposed on trimodality therapy, are unknown.
Based on the data and NCCN guidelines, yes for immunotherapy (atezolizumab) and no for durvalumab.
For superior sulcus tumors with T3 invasion and N0-1 nodal involvement, preoperative concurrent chemoradiation followed by surgery plus adjuvant chemotherapy and atezolizumab or osimertinib (depending on biomarker status EGFR exon 19 deletion or L858 R) is recommended.
For stage IIIA superior sulcus tumors with T4 extension and N0-1 nodal status, if they become resectable after preoperative concurrent chemoradiation, surgical resection followed by chemotherapy then followed by atezolizumab or osimertinib (depending on biomarker status EGFR exon 19 deletion or L858 R) is recommended.
If tumor remains unresectable following preoperative concurrent chemoradiation, then completion of definitive chemoradiation followed by immunotherapy with durvalumab is recommended.
Durvalumab is not recommended for patients following definitive surgical resection.
NCCN Guidelines Version 3. 2022 Non-Small Cell Lung Cancer NSCLC-6