Recent phase III data suggest meaningful first-line practice shifts in metastatic breast cancer. DESTINY-Breast09 and ASCENT-04/KEYNOTE-D19 show that modern antibody–drug conjugates paired with targeted agents can improve progression-free survival and reduce toxicity compared with chemotherapy in HER2-positive and PD-L1–positive triple-negative disease. SERENA-6 demonstrates that switching to camizestrant at the time of ESR1 mutation detection — before radiographic progression — can prolong PFS in HR-positive/HER2-negative disease. INAVO120 similarly supports adding inavolisib to palbociclib and fulvestrant for PIK3CA-mutant tumors, delaying the need for chemotherapy. Together, these trials underscore a move toward more precise, mutation-guided first-line strategies.

Looking ahead, one trend that deserves far greater attention is minimal residual disease monitoring with ctDNA to guide adjuvant escalation or de-escalation. As assays become more sensitive and standardized, MRD has real potential to supersede traditional risk factors and enable a truly individualized, response-adaptive approach in early breast cancer.

Ana Tecic Vuger

University Hospital Centre Zagreb, Croatia

Michael K Gibson

Vanderbilt-Ingram Cancer Center, Vanderbilt University Medical Center, Nashville, TN, USA

Lung cancer remains the number one cause of cancer death worldwide.¹ However, the management of lung cancer continues to change year-by-year, with significant progress in both small‑cell (SCLC) and non–small cell lung cancer (NSCLC). In 2025, ASCO and ESMO presented trials demonstrating the benefits of targeted therapies, bispecific antibodies, and combination approaches. In advanced stage SCLC, the Phase III DeLLphi-304 trial (ClinicalTrials.gov number, NCT05740566) showed that Tarlatamab, a DLL3-directed bispecific T-cell engager, significantly improved overall survival (OS) compared with standard chemotherapy (median OS 13.6 vs 8.3 months; HR 0.60) in whose disease had progressed during or after platinum-based chemotherapy. In NSCLC, the Phase III MARIPOSA trial (ClinicalTrials.gov number, NCT04487080) established that the combination of Amivantamab plus Lazertinib is better than Osimertinib monotherapy in EGFR-mutated (ex19del/L858R) patients, over a median follow-up of 37.8 months, amivantamab–lazertinib led to significantly longer OS than osimertinib (HR for death, 0.75; 95% CI, 0.61 to 0.92; P=0.005). Additionally, Sevabertinib received accelerated FDA approval for patients with HER2-mutant non-squamous NSCLC after prior systemic therapy, based on SOHO-01 trial (ClinicalTrials.gov number, NCT05099172) results. The SOHO-01 trial showed a 71% objective response rate (ORR) in patients who had received prior systemic therapy but were naive to therapy targeting HER2 mutations and a 38% ORR in those previously treated with prior systemic therapy including HER2-targeted antibody drug conjugates.² Bispecific antibodies and targeted therapies are increasingly demonstrating superiority over monotherapy, reinforcing the importance of comprehensive molecular profiling and individualized treatment planning. As new agents move from trials to clinical practice, ongoing research will clarify optimal sequencing and integration, ultimately improving outcomes for patients with both SCLC and NSCLC.

Gabriel Lenz

AdventHealth, Orlando, FL, USA