August delivered a compact but meaningful set of oncology updates: two U.S. FDA accelerated approvals and several practice-informing papers across skin, lung, head & neck, kidney, colorectal, breast, and hematologic cancers.
Lung cancer
1) HER2-mutant NSCLC — zongertinib wins FDA accelerated approval
- What happened: The FDA granted accelerated approval to zongertinib (Hernexeos) for adults with unresectable or metastatic non-squamous NSCLC harboring HER2 (ERBB2) tyrosine-kinase-domain activating mutations after prior systemic therapy. Approval was based on tumor response rate and durability from a multicenter trial; testing must use an FDA-approved assay.
- Why it matters: This is a targeted option for a genomically defined slice of NSCLC that, until recently, had few dedicated TKIs. It formalizes HER2 TKD mutations as a clinically actionable biomarker in lung cancer.
- Key takeaways:
- Check HER2 TKD status on progression—patients may now have a path to a HER2-selective TKI.
- The label is post-prior therapy and under accelerated framework → confirmatory data still needed.
- Further reading: FDA label/summary. U.S. Food and Drug Administration
2) KRAS G12C NSCLC — adagrasib bests docetaxel in phase 3 (KRYSTAL-12)
- What happened: The Lancet published the randomized KRYSTAL-12 trial, where adagrasib showed superior progression-free survival and response rate vs docetaxel in previously treated KRAS G12C–mutant NSCLC. OS is maturing.
- Why it matters: Confirms a KRAS G12C inhibitor can outperform chemo in a head-to-head phase 3 setting post-immunotherapy, strengthening the case for targeted sequencing of KRAS.
- Key takeaways:
- Expect more KRAS G12C inhibitor use beyond single-arm data; watch for safety/tolerability tradeoffs vs docetaxel.
- OS follow-up will shape guidelines and reimbursement.
- Further reading: The Lancet paper and ESMO news analysis. The Lancet
Brain tumors
3) Diffuse midline glioma (H3 K27M-mutant) — dordaviprone (Modeyso) earns FDA accelerated approval
- What happened: The FDA approved dordaviprone, a protease activator, for adult and pediatric patients ≥1 year with H3 K27M–mutant diffuse midline glioma with progression after prior therapy—the first approved treatment for this ultra-rare, aggressive disease. Integrated data included objective responses with meaningful duration.
- Why it matters: Until now, there were no approved therapies for recurrent H3 K27M DMG; management was largely palliative. This is a genuine line-in-the-sand moment for neuro-oncology and pediatric oncology.
- Key takeaways:
- Companion testing for H3 K27M is essential.
- Approval is accelerated → clinicians should discuss uncertainty and the need for confirmatory trials with families.
- Further reading: FDA summary; National Brain Tumor Society explainer; industry clinical metrics. U.S. Food and Drug Administration
Head & neck (nasopharyngeal carcinoma)
4) Cisplatin-sparing concurrent therapy — toripalimab-containing regimen shows high efficacy with lower toxicity
- What happened: JAMA highlighted a phase 3 randomized study testing toripalimab without concurrent cisplatin during chemoradiation for locoregionally advanced nasopharyngeal carcinoma. The trial reported strong failure-free survival and less toxicity, making a case that cisplatin-free concurrent immunotherapy-based strategies can be feasible.
- Why it matters: Standard concurrent cisplatin adds significant toxicity. If validated across settings, cisplatin-sparing protocols could reshape supportive care demands while maintaining disease control.
- Key takeaways:
- Not yet a universal standard; practice change will hinge on peer-review details, OS, and guideline uptake.
- Fits a broader trend: peri-CRT immunotherapy in NPC.
- Further reading: JAMA editor’s highlights; summary (with DOI reference). JAMA
Skin cancer
5) Cutaneous SCC (resected, high risk) — adjuvant cemiplimab gets its NEJM moment (Aug 21)
- What happened: NEJM published the C-POST randomized trial: adjuvant cemiplimab vs placebo after surgery (± RT) in high-risk cutaneous SCC. Cemiplimab prolonged disease-free survival and reduced recurrence risk.
- Why it matters: There has been no established adjuvant systemic therapy for this common, high-recurrence skin cancer. These data are practice-shaping and could be guideline-setting once regulators finish reviewing.
- Key takeaways:
- Expect rising PD-1 use post-resection in high-risk features cohorts.
- Mind immune-related AEs; counseling remains key.
- Further reading: NEJM slide deck & CME page; trial protocol citation confirms article details. New England Journal of Medicine
Kidney cancer
6) First-line ccRCC — KEYNOTE-426 5-year final analysis in Nature Medicine (Aug 1)
- What happened: The 5-year survival and biomarker analysis of pembrolizumab + axitinib vs sunitinib in untreated clear-cell RCC confirmed durable, sustained benefit of the combo and explored biomarker signatures that may guide selection.
- Why it matters: Long-horizon outcomes solidify the regimen’s place in first-line RCC and feed the biomarker hunt to refine immuno-TKI choices.
- Key takeaways:
- Long-term OS/PFS advantage is credible at 5 years; this is not a transient effect.
- Biomarker work is exploratory—not ready to drive routine selection yet.
- Further reading: Nature Medicine paper and institutional news summary. NatureVUMC News
Colorectal cancer
7) KRAS G12C mCRC — HRQoL with sotorasib + panitumumab looks better than SOC (CodeBreaK 300)
- What happened: The Lancet Oncology published patient-reported outcomes from CodeBreaK 300, showing better health-related quality of life with sotorasib + panitumumab vs trifluridine/tipiracil or regorafenib in chemorefractory KRAS G12C mCRC.
- Why it matters: We’ve seen efficacy signals previously; PROs now suggest the targeted doublet may feel better to patients than late-line chemo options—useful in shared decision-making.
- Key takeaways:
- For eligible KRAS G12C mCRC, expect more PRO-informed conversations favoring the targeted combo when available.
- Access, sequencing after prior biologics, and payer rules will influence use.
- Further reading: The Lancet Oncology paper and ASCO Post summary. The Lancet
Breast cancer
8) Extended endocrine therapy — patient-level meta-analysis across 12 trials (EBCTCG)
- What happened: The Lancet published an EBCTCG meta-analysis (22,031 postmenopausal women) showing that extending aromatase inhibitor therapy beyond 5 years yields additional recurrence risk reduction; the absolute benefit varies by baseline risk.
- Why it matters: It sharpens the risk/benefit calculus on 7–10 years of AI therapy—underscoring the need to individualize based on recurrence risk and tolerance.
- Key takeaways:
- Discuss fracture/metabolic risks and patient preferences; benefit is real but heterogeneous.
- May influence clinic policy on systematic risk stratification before extending therapy.
- Further reading: The Lancet meta-analysis. The Lancet
Hematologic malignancies
9) ALL (adult, R/R) — subcutaneous blinatumomab shows promising activity (early-phase)
- What happened: The Lancet Haematology reported phase 1 dose-finding results with subcutaneous blinatumomab in relapsed/refractory B-ALL showing promising activity with a manageable safety profile; phase 2 is ongoing.
- Why it matters: SC administration could simplify delivery of a drug that’s traditionally continuous IV, potentially improving patient experience and resource use if efficacy holds.
- Key takeaways:
- Not practice-changing yet—but one to watch as later-phase data mature.
- Further reading: The Lancet Haematology report. The Lancet
10) AML/MDS (post-HSCT, very high-risk) — oral decitabine/cedazuridine as maintenance (phase 2)
- What happened: A multicenter phase 2 study evaluated oral decitabine/cedazuridine maintenance after transplant in very high-risk AML/MDS, suggesting feasible activity that merits further evaluation.
- Why it matters: Post-HSCT relapse remains the crux problem; oral hypomethylator maintenance—if confirmed—could offer a pragmatic prophylactic option.
- Key takeaways:
- Consider trial enrollment where available; evidence is non-randomized at this stage.
- Further reading: The Lancet Haematology abstract. The Lancet
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