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The phase II trial of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy in borderline resectable and unresectable stage III NSCLC showed a significant improvement in event-free survival (EFS) with the combination (24.1 vs 10.6 months) compared to chemotherapy alone, with a hazard ratio (HR) of 0.62. Major pathological response rates were higher with immunotherapy (44.7% vs 22.3%), and no new safety signals were noted. The regimen improved surgical resection rates (68% vs 52%) without increasing perioperative complications. This validates chemoIO in the neoadjuvant setting particularly in whom we wish to pursue resection or avoid chemoradiation. It would be great to see this compared to chemoradiation followed by immunotherapy rather than chemotherapy alone.

Dato showed a confirmed overall response rate (ORR) of 42.7% with a complete response (CR) of 4.3%. The median duration of response was 7.0 months, with a disease control rate of 86.3% and a median overall survival (OS) of 15.6 months. This could be another option for EGFR mutant patients who had multiple lines of therapy.

Results showed the median event-free survival (EFS) was 54.8 months with nivolumab plus ipilimumab vs 20.9 months with chemotherapy. Three-year EFS rates were 56% vs 44%. Three-year overall survival (OS) rates were 73% vs 61% pathologic complete response rates were 20.4% vs 4.6%. This was three cycles of nivolumab and one dose of ipilimumab vs chemotherapy.

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).

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?

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.

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.

Pembrolizumab in addition to chemotherapy DID NOT help, recall now we have new approval for those patients (datopotamab).

Superior to osi (23 vs 16 progression-free survival). This is more toxic though, but seems manageable. Could this be a new first line standard of care? Also, this includes brain penetration data.