Novinky z X/Twitteru - výběr zajímavých recentních publikací a výsledků studií 10-11/23

  • (LF MU a FN Brno, Interní hematologická a onkologická klinika)

Sekce mladých onkologů pravidelně zpřístupňuje pro své členy výsledky z nových studií, novinky či zajímavé přehledové články napříč diagnózami na sociální síti X, dříve Twitter. Pro ty, co nemají přístup na tuto sociální síť, zveřejňujeme v pravidelných intervalech nejzajímavější informace přímo zde. Dnes novinky z Twitteru za říjen a listopad. 

Dacomitinib in EGFR-mutant non-small-cell lung cancer with brain metastasis: a single-arm, phase II study 

https://doi.org/10.1016/j.esmoop.2023.102068 

  • The confirmed iORR was 96.7% (29/30), with an intracranial complete response of 63.3%. 
  • Median iPFS was not reached, with 12- and 18-month iPFS rates of 78.6% and 70.4%, respectively. 
  • In the competing risk analysis, the 12-month cumulative incidence of intracranial progression was 16.7%.  

Efficacy and Safety of Trastuzumab Deruxtecan in Patients With HER2-Expressing Solid Tumors: Primary Results From the DESTINY-PanTumor02 Phase II Trial

https://ascopubs.org/doi/full/10.1200/JCO.23.02005?role=tab 

  • 267 pretreated patients with HER2-expressing (3+/2+) tumors receiving trastuzumab deruxtecan 
  • For general population -> ORR 37.1%, DOR 11.3m, PFS 6.9m, mOS 13.4m 
  • For HER 2 IHC 3+ -> ORR 61.3%, mDOR 22.1m, mOS 21.1m 

Efficacy and Safety of Disitamab Vedotin in Patients With Human Epidermal Growth Factor Receptor 2–Positive Locally Advanced or Metastatic Urothelial Carcinoma: A Combined Analysis of Two Phase II Clinical Trials 

https://ascopubs.org/doi/10.1200/JCO.22.02912 

  • 107 patients, least one previous line CHT -> ORR 50.5%, PFS 5.9m, OS 14.2m, > G3 AE 54.2% (neuropathy 19%)   

Clinical and Biomarker Findings of Neoadjuvant Pembrolizumab and Carboplatin Plus Docetaxel in Triple-Negative Breast Cancer NeoPACT Phase 2 Clinical Trial 

 https://jamanetwork.com/journals/jamaoncology/article-abstract/2812294  

  • Neoadjuavnt Carbo/Docetaxel/Pemro x6 led to a pCR rate of 58% and 3y EFS of 86% for stage I-III TNBC. Confirmatory phase III SCARLET trial ongoing 

Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC 

https://www.nejm.org/doi/full/10.1056/NEJMoa2306434?query=featured_home 

  • A total of 557 patients underwent randomization. Investigator-assessed progression-free survival was significantly longer in the osimertinib–chemotherapy group than in the osimertinib group (hazard ratio for disease progression or death, 0.62; 95% confidence interval [CI], 0.49 to 0.79; P<0.001). At 24 months, 57% (95% CI, 50 to 63) of the patients in the osimertinib–chemotherapy group and 41% (95% CI, 35 to 47) of those in the osimertinib group were alive and progression-free.  
  • Progression-free survival as assessed according to blinded independent central review was consistent with the primary analysis (hazard ratio, 0.62; 95% CI, 0.48 to 0.80).  
  • An objective (complete or partial) response was observed in 83% of the patients in the osimertinib–chemotherapy group and in 76% of those in the osimertinib group 
  • The median response duration was 24.0 months (95% CI, 20.9 to 27.8) and 15.3 months (95% CI, 12.7 to 19.4), respectively.  

Oncological outcomes of standard versus prolonged time to surgery after neoadjuvant chemoradiotherapy for oesophageal cancer in the multicentre, randomised, controlled NeoRes II trial 

https://doi.org/10.1016/j.annonc.2023.08.010 

  • The optimal timing of surgery after completed nCRT for oesophageal cancer is not known. 
  • Merely based on observational studies clinical practice has moved towards prolonged delay of surgery for up to 12 weeks. 
  • This randomised controlled trial compared standard 4-6 weeks’ TTS to prolonged delay of 10-12 weeks. 
  • No significant differences in histological complete response, tumour regression or complete tumour resections were found. 
  • A strong trend of worse overall survival was found after prolonged TTS, suggesting caution in routinely delaying surgery. 

Practice Guidelines for Resectable, Borderline Resectable, and Locally Advanced Pancreas Cancer 2023 – Annals of Surgical Oncology 

https://link.springer.com/article/10.1245/s10434-023-14585-y 

Systemic therapy with or without local intervention for oligometastatic oesophageal squamous cell carcinoma (ESO-Shanghai 13): an open-label, randomised, phase 2 trial 

https://doi.org/10.1016/S2468-1253(23)00316-3

  • The addition of local treatment for 1-4 metastases significantly improves PFS among patients with oligometastatic oesophageal squamous cell carcinoma being treated with systemic therapy 
  • 15.3 vs. 6.4m 
  • MDT discussion necessary 

ESTRO clinical practice guideline: Stereotactic body radiotherapy for spine metastases 

https://www.thegreenjournal.com/article/S0167-8140(23)89860-7/fulltext 

  • This ESTRO clinical practice guideline provides evidence-based recommendations and statements regarding the selection of patients with spinal metastases for SBRT and its safe implementation and practice. Enrollment of patients into well-designed prospective clinical trials addressing clinically relevant questions is considered important. 

Pretreatment albumin is a prognostic and predictive biomarker for response to atezolizumab across solid tumors 

https://onlinelibrary.wiley.com/doi/10.1002/cti2.1472 

  • A total of 3391 patients were analysed. Correlation between serum albumin and atezolizumab levels was weak (Pearson's coefficient 0.23). We found a strong prognostic value for pretreatment serum albumin across all trials. Both atezolizumab serum levels and serum albumin were independently correlated with overall survival. Importantly, in the three randomised phase III clinical trials, the survival benefit for immunotherapy compared with the active comparator arm was limited to patients with pretreatment serum albumin > 35 g /L. 

HER2-low heterogeneity between primary and paired recurrent/metastatic breast cancer: Implications in treatment and prognosis 

https://acsjournals.onlinelibrary.wiley.com/doi/10.1002/cncr.35101 

  • In total, 370 patients (28.5%) experienced primary-to-metastatic HER2 conversion. Intrapatient intermetastasis spatial heterogeneity and temporal heterogeneity of HER2 were detected. When assessing HER2 based on recurrent/metastatic tumors, patients who had HER2-0 tumors had significantly shorter overall survival than those who had HER2-low tumors in the overall population and in the estrogen receptor (ER)-negative subgroup. However, when assessing HER2 based on primary tumors, there was no difference in overall survival between patients who had HER2-0 versus HER2-low tumors. Moreover, patients who had tumors that converted from HER2-0 to HER2-low had longer overall survival than those who had consistent HER2-0 status in the ER-negative subgroup. By combining four predictors (ER status, Ki67 index, biopsy site, and disease-free interval), the authors established the first prediction tool to estimate the probability of HER2-0 tumors converting to HER2-low/positive tumors. 

Long-Term Results of Organ Preservation in Patients With Rectal Adenocarcinoma Treated With Total Neoadjuvant Therapy: The Randomized Phase II OPRA Trial 

https://ascopubs.org/doi/10.1200/JCO.23.01208 

  • In total, 324 patients were randomly assigned (INCT-CRT, n = 158; CRT-CNCT, n = 166). Median follow-up was 5.1 years. The 5-year DFS rates were 71% (95% CI, 64 to 79) and 69% (95% CI, 62 to 77) for INCT-CRT and CRT-CNCT, respectively (P = .68). TME-free survival was 39% (95% CI, 32 to 48) in the INCT-CRT group and 54% (95% CI, 46 to 62) in the CRT-CNCT group (P = .012). Of 81 patients with regrowth, 94% occurred within 2 years and 99% occurred within 3 years. DFS was similar for patients who underwent TME after restaging (64% [95% CI, 53 to 78]) and patients in WW who underwent TME after regrowth (64% [95% CI, 53 to 78]; P = .94). Updated analysis continues to show long-term organ preservation in half of the patients with rectal cancer treated with total neoadjuvant therapy. In patients who enter WW, most cases of tumor regrowth occur in the first 2 years. 

Resistance mechanism to fibroblast growth factor receptor (FGFR) inhibitors in cholangiocarcinoma 

https://doi.org/10.1016/j.ctrv.2023.102627 

  • Molecular profiling of CCA has identified targetable alterations. 
  • FGFR-2 fusions are targeted by a variety of new compounds. 
  • Primary resistance is still an issue for a proportion of patients. 
  • Mechanism of secondary resistance are being defined and better understood.