No abstract

These changes in the processing of miRNAs have great value in pathology diagnosis, including lung diseases, and play an important role in the understanding of molecular mechanisms involved in the development of different pathologies, as well as representing new therapeutic targets.

No abstract

LBA506 Background: PHERGain is assessing the feasibility of a CT-free treatment based on a dual HER2 blockade with trastuzumab and pertuzumab (HP) in patients (pts) with HER2[+] EBC using a PET-based, pathologic complete response (pCR)-adapted strategy. In an earlier analysis of this study, a total of 227 (79.7%) of 285 pts included in group B were PET-responder (RX), of whom 86 of 227 (37.9%, 95% CI, 31.6 to 44.5; p<0.0001) achieved a pCR, reaching the first primary endpoint (Perez-Garcia JM, Lancet Oncol 2021). Methods: Details of the trial design and study population have been previously reported. Here, we present the results of the second primary endpoint, 3-year iDFS, among pts included in group B who underwent surgery based on an intent-to-treat (ITT) analysis. In brief, group B included centrally-confirmed, stage I-IIIA, HER2[+] EBC pts that were initially treated with HP (± endocrine therapy), introducing CT in pts without PET response after two treatment cycles and/or pCR. The binomial design tested the null hypothesis that the true 3-year iDFS rate was ≤89.0% against the alternative that the 3-year iDFS was >95%. We estimated that enrolling 284 pts in group B would provide 80% power at a nominal level of one-sided α of 0.025, assuming a 25% dropout rate. Results: Between June 26, 2017 and April 24, 2019, 356 pts were randomly assigned (71 pts in group A and 285 pts in group B) and 63 (89.0%) and 267 (93.7%) pts proceeded to surgery in groups A and B, respectively. In group B, the 3-year iDFS rate for the ITT population was 95.4% (95% CI, 92.8 to 98), meeting the second primary endpoint (p<0.001). After a median follow-up of 43.3 months (range, 2.4-63.0), a total of 12 iDFS events were reported, including eight distant recurrences (3.0%), three locoregional ipsilateral recurrences (1.1%), and one non-related death (0.4%). Among group B/PET-RX pts with pCR that did not receive CT as part of study treatment (n = 86), only one patient had an invasive event (locoregional ipsilateral recurrence) for a 3-year iDFS rate of 98.8% (95% CI, 96.3 to 100.0). Treatment-related adverse events (AEs) and serious adverse events (SAEs) were higher in pts allocated to group A than to group B (grade ≥3, 61.8% vs. 32.9% [p<0.001]; SAEs, 27.9% vs. 13.8% [p=0.01]). Group B/PET-RX pts with pCR presented the lowest incidence of treatment-related grade ≥3 AEs (1.2%) without any SAEs. No treatment-related deaths were reported. Conclusions: Among HER2[+] EBC pts, a PET-based, pCR-adapted strategy was associated with a substantial 3-year iDFS. These results appear comparable to those reported in several studies for the combination of neoadjuvant CT and dual HER2 blockade. This strategy identifies about a third of HER2[+] EBC pts who may safely omit CT with significantly reduced toxicity. Clinical trial information: NCT5732164 .