The Phase III trial enrolled 948 patients with stage II–IVA resectable GC/GEJC, randomized 1:1 to durvalumab plus FLOT vs placebo plus FLOT. Treatment included four neoadjuvant and four adjuvant cycles of FLOT, with durvalumab or placebo co‑administered, followed by up to 10 cycles of durvalumab or placebo maintenance. With a median follow‑up of ~31.5 months, median event-free survival (EFS) was not reached in the durvalumab arm versus 32.8 months with placebo (HR 0.71, 95% CI 0.58–0.86; p < 0.001). Two‑year EFS was notably higher: 67.4% vs 58.5%. Interim overall survival favored durvalumab (HR 0.78; p = 0.025; data ~33% mature). Grade 3/4 adverse events (AEs) occurred in ~60% of both arms. Most frequent toxicities included neutropenia, diarrhea, nausea, alopecia, and decreased appetite. Importantly, durvalumab did not delay surgery or adjuvant treatment. ¹

Yelena Janjigian, MD, Memorial Sloan Kettering Cancer Center, New York, NY, comments on the significance of the MATTERHORN study:
“The MATTERHORN study shows that adding immunotherapy before surgery helps suppress micrometastasis and improves survival, without delaying surgery or adding unexpected toxicity.”

MATTERHORN marks the first global Phase III trial to show that perioperative durvalumab significantly improves EFS in resectable GC/GEJC, setting a new standard of care. The durability of EFS benefit, favorable safety, and seamless integration into surgical timelines reinforce its practice-changing potential. Overall survival data remain immature but show promising trends. Pending regulatory decisions, durvalumab plus FLOT is positioned to redefine perioperative management in fit patients with resectable disease. ²

Christian Singer, MD, MPH, Medical University of Vienna, Vienna, Austria, comments on the Destiny Breast 09 trial:
“DESTINY-Breast09 is remarkable—we see better long-term outcomes and improved progression-free survival with trastuzumab deruxtecan plus pertuzumab compared to the traditional standard. It’s a real step forward.”

While overall survival (OS) data are still maturing, early signals suggest a positive trend (HR 0.84). Subgroup analyses showed consistent benefit across hormone receptor subtypes and presence of visceral disease. ⁴

In conclusion, DESTINY‑Breast09 establishes the potent efficacy of first‑line T‑DXd plus pertuzumab in HER2‑positive metastatic breast cancer. With unprecedented PFS nearing 41 months, improved response durability, and a manageable safety profile, this combination presents a compelling alternative to THP. Pending full OS data and regulatory reviews, it has the potential to redefine standard-of-care in this setting.

At a median follow-up of 41.9 months, the pembrolizumab arm demonstrated a 28% reduction in the risk of disease progression or death compared to the placebo arm (HR 0.72; 95% CI, 0.59–0.87). The 36-month PFS rate was 70.6% with pembrolizumab versus 59.7% with placebo. OS results were similarly favorable, with a 27% reduction in the risk of death (HR 0.73; 95% CI, 0.57–0.94). The 36-month OS rates were 81.8% and 74.4%, respectively, and the 48-month OS was 75.4% for pembrolizumab compared to 70.2% for placebo. Efficacy was consistent across key subgroups, including patients with node-positive stage IB2–IIB disease and stage III–IVA cancer. However, the survival benefit was less pronounced in patients aged ≥65, warranting further investigation

Treatment-related adverse events (TRAEs) occurred in nearly all patients in both arms (97% pembrolizumab vs. 96.8% placebo), with grade ≥3 events more frequent in the pembrolizumab group (69.5% vs. 61.5%). Immune-mediated AEs were more common with pembrolizumab (39.8% vs. 17.5%) but largely manageable. Two deaths attributed to TRAEs occurred in each arm, and no new safety concerns were identified.

Jyoti Mayadev, MD, University of California San Diego Medical Center, San Diego, CA, on KEYNOTE-A18:
“At three years, we still see separation in progression-free and overall survival curves—showing a clear benefit for pembrolizumab during and after chemoradiation in locally advanced cervical cancer.”

The final analysis from KEYNOTE-A18 establishes pembrolizumab plus CCRT followed by maintenance therapy as a new global standard for high-risk locally advanced cervical cancer.  With statistically and clinically meaningful gains in both PFS and OS, the trial redefines curative-intent management in this patient population. Ongoing studies aim to refine patient selection and evaluate long-term outcomes.

Marcelo Corassa, MD, A.C. Camargo Cancer Center, São Paulo, Brazil, on SOHO-01:
“These patients have an unmet need, and sevabertinib showed a 59–60% response rate, giving us another option after trastuzumab deruxtecan.”

Following these results, the FDA has accepted sevabertinib’s New Drug Application under Priority Review for previously treated HER2-mutant NSCLC. The Phase III trial SOHO‑02 trial (NCT06452277) is now underway comparing sevabertinib to chemotherapy plus pembrolizumab in the first-line setting. ⁷

In summary, SOHO‑01 delivers compelling evidence of sevabertinib’s potent antitumor activity and acceptable tolerability in HER2‑mutant NSCLC. With Phase III validation and regulatory review underway, sevabertinib may soon offer a new standard of care for this distinct molecular subgroup.