#ESMO26 | Our Meta-Analysis
Another study conducted with Rohit and Rahul (@OncBrothers )!
BRAF/MEK inhibition vs ICI-based therapy in first-line BRAF V600E-mutant metastatic NSCLC.
Our meta-analysis included 4 retrospective studies involving 589 patients.
🔹PFS: HR 1.22 (95% CI 0.89–1.68; p=0.22)
🔹OS: HR 1.01 (95% CI 0.59–1.73; p=0.97)
🔹ORR: 65.3% vs 48.0%, favoring BRAF/MEK inhibition (p=0.04).
BRAF/MEK inhibition achieved higher response rates without a statistically significant survival advantage.
I suspect most clinicians will continue to prioritize BRAF/MEK inhibition, particularly in light of the impressive PHAROS results.
However, the optimal first-line strategy remains an open question, and our findings highlight the need for prospective comparative evidence.
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NRG-GY020: Phase III randomized trial of radiation +/- MK-3475 (pembrolizumab) for newly diagnosed early-stage high intermediate risk (HIR) mismatch repair deficient (dMMR) endometrioid endometrial cancer
https://esmocongress.esmo.orgSacituzumab tirumotecan (Sac-TMT) + pembrolizumab (Pembro) in post-platinum advanced mismatch repair proficient (pMMR) endometrial cancer (EC)
https://esmocongress.esmo.orgSTARBOARD phase 3: A randomized, double-blind study of first-line (1L) encorafenib (enco), binimetinib (bini), and pembrolizumab (pembro) vs placebo (pbo) and pembro for unresectable locally advanced or metastatic BRAF V600-mutant melanoma
https://esmocongress.esmo.orgEfficacy and safety of lifileucel and pembrolizumab in patients with immune check point inhibitor-naïve advanced melanoma: Final results from IOV-COM-202 study
https://esmocongress.esmo.orgUpdated results from the phase 1b/2 KEYNOTE-365 cohort I: Pembrolizumab (pembro) + carboplatin and etoposide chemotherapy (chemo) or chemo alone for neuroendocrine prostate cancer (NEPC)
https://esmocongress.esmo.orgFirst-line (1L) olomorasib + pembrolizumab in KRAS G12C-mutant NSCLC: Updated results from LOXO-RAS-20001 and SUNRAY-01
https://esmocongress.esmo.org- Yakup Ergün@dr_yakupergun
I don't consider TMB alone a reliable predictive biomarker in MSS colorectal cancer. Particularly after treatment, an increase in TMB may reflect the accumulation of subclonal mutations rather than sensitivity to immunotherapy. Outside specific molecular subgroups such as POLE/POLD1 proofreading-deficient tumors, we lack convincing evidence to support immunotherapy based solely on high TMB. However, when standard treatment options have been exhausted, immunotherapy may be considered, particularly in patients with markedly elevated TMB, while acknowledging the limited evidence.
- Asil0707@asill7007
Hi Doctor, regarding the recent October 2026 FDA approval update for Keytruda in TMB-High solid tumors: For a heavily pretreated metastatic colorectal cancer patient (MSS/MSI-negative, prior therapies, Pembrolizumab-naive) with a TMB of 16, would you consider Keytruda a viable option? What would be your clinical approach if this were your patient? Thanks!
Source: Yakup Ergün · x.com