This is a small trial but really promising in patients with tumors expressing PDL-1 > 50%. We need larger randomized trials and longer follow up.
Look at the rate of controlled release (CR) just by induction therapy. Do we really need radiation for those patients? This should be another area to study.
Thoughts from radiation oncologists are welcomed.
Standard therapy for locally advanced non–small-cell lung cancer (LA-NSCLC) is concurrent chemoradiotherapy followed by adjuvant durvalumab. For biomarker-selected patients with LA-NSCLC, we hypothesized that sequential pembrolizumab and risk-adapted radiotherapy, without chemotherapy, would be well-tolerated and effective.
Patients with stage III NSCLC or unresectable stage II NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible for this trial. Patients with a PD-L1 tumor proportion score (TPS) of ≥50% received three cycles of induction pembrolizumab (200 mg, once every 21 days), followed by a 20-fraction course of risk-adapted thoracic radiotherapy (55 Gy delivered to tumors or lymph nodes with metabolic volume exceeding 20 cc, 48 Gy delivered to smaller lesions), followed by consolidation pembrolizumab to complete a 1-year treatment course. The primary study end point was 1-year progression-free survival (PFS). Secondary end points included response rates after induction pembrolizumab, overall survival (OS), and adverse events.
Twenty-five patients with a PD-L1 TPS of ≥50% were enrolled. The median age was 71, most patients (88%) had stage IIIA or IIIB disease, and the median PD-L1 TPS was 75%. Two patients developed disease progression during induction pembrolizumab, and two patients discontinued pembrolizumab after one infusion because of immune-related adverse events. Using RECIST criteria, 12 patients (48%) exhibited a partial or complete response after induction pembrolizumab. Twenty-four patients (96%) received definitive thoracic radiotherapy. The 1-year PFS rate is 76%, satisfying our efficacy objective. One- and 2-year OS rates are 92% and 76%, respectively. The most common grade 3 adverse events were colitis (n = 2, 8%) and esophagitis (n = 2, 8%), and no higher-grade treatment-related adverse events have occurred.
Pembrolizumab and risk-adapted radiotherapy, without chemotherapy, are a promising treatment approach for patients with LA-NSCLC with a PD-L1 TPS of ≥50%.
Patients were treated with thoracic and extrathoracic radiation to oligometastatic sites and it seems to help with improving survival, something to consider especially with SBRT now. Do our radiation oncologists have additional input?
Improved progression-free survival (PFS), now we have osimertinib and ramucirumab, amivantamab and Lazertinib (PFS 24.8 vs 23 months but NOT head to head).
Very thought-provoking review of immune checkpoint blockade therapy and strategies to possibly de-escalate therapy in the future. Could we reduce doses, extend dose intervals or diminish the duration of treatment? There is some (low-level) data supporting these ideas. However, ongoing prospective studies, mostly being done in countries with nationalized systems, will be informative on these topics. Expect interest in this topic to increase in a couple of years.
Positive trial for the newest ADC on the block, Dato-DXd, is an ADC that delivers a topoisomerase I inhibitor payload via a TROP2 antibody. PFS was not impressive but favored DDxd at 4.4 vs 3.7 months in the docetaxel arm. This drug is now approved in metastatic breast cancer.
Pembrolizumab in addition to chemotherapy DID NOT help, recall now we have new approval for those patients (datopotamab).
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