Key sessions

• Presidential Symposium I — Saturday 24 October, 16:30–18:15 CEST (20:00–21:45 IST), Alicante Auditorium, Hall 6. Late-breaking abstracts span melanoma, bladder cancer, small-cell lung cancer and high-risk prostate cancer.
• Presidential Symposium II — Sunday 25 October, 16:30–18:15 CET (21:00–22:45 IST), same venue, covering NSCLC, gastric and biliary-tract cancers.

The programme also includes sessions on artificial intelligence in oncology, toxicities of novel therapies and patient-advocacy sessions on access and equity — topics highly relevant to public-sector oncology in India.

I will post short summaries of the practice-changing results here after the data are presented. Abstracts are available through the official ESMO programme linked below.

Why it matters

Two approvals (atezolizumab in colon cancer, dostarlimab in rectal cancer) reinforce universal MMR/MSI testing of colorectal cancers at diagnosis — something we can do with immunohistochemistry in most centres.

These are US FDA decisions. Approval and availability in India (CDSCO) may differ.

Background

About 5–10% of rectal cancers are mismatch-repair deficient. The landmark single-centre study from Memorial Sloan Kettering (Cercek et al., NEJM 2022) reported that the first 12 patients treated with dostarlimab alone had a clinical complete response, avoiding chemoradiation and surgery at the time of reporting.

For patients

If you have rectal cancer, ask whether your biopsy has been tested for MMR (mismatch repair) or MSI. The result can change which treatment is best.

Accelerated approval means continued approval may depend on confirmatory trials. This is a US decision.

• Phase 3, n=914. Arms: trastuzumab + chemo (A), zanidatamab + chemo (B), zanidatamab + tislelizumab + chemo (C). Mandatory antidiarrhoeal prophylaxis.
• PFS: 8.1 (A) vs 12.4 (B; HR 0.65) vs 12.4 mo (C; HR 0.63).
• OS (interim): 19.2 vs 24.4 (HR 0.80, p=0.056, not significant) vs 26.4 mo (HR 0.72, p=0.0043).
• Grade ≥3 AEs: 60% / 59% / 72%. Diarrhoea the main toxicity.

BREAKWATER — BRAF V600E mCRC (first line)

Encorafenib + cetuximab + FOLFIRI improved outcomes vs FOLFIRI + bevacizumab (Abstract 13), extending the earlier FOLFOX-based result that led to FDA accelerated approval. I have not verified the exact hazard ratios for the FOLFIRI cohort; see ASCO Daily News link.

COMMIT — dMMR/MSI-H mCRC

n=102 (randomised phase 3; chemo-bev arm closed after KEYNOTE-177). mFOLFOX6 + bevacizumab + atezolizumab vs atezolizumab alone: median PFS 24.5 vs ~5 mo; ORR 86.1% vs 46%. More grade ≥3 AEs (34 vs 18 patients) and grade 5 events (4 vs 1).

COMMIT's single-agent arm PFS looks low compared with KEYNOTE-177/CheckMate-8HW; I would not abandon IO-only (or nivolumab–ipilimumab) for dMMR mCRC on this trial alone.

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

Phase 3, open-label, 147 sites. High-risk HER2+ early breast cancer (≥T3, node-positive or inflammatory). Arms: T-DXd ×8 (closed early), T-DXd ×4 → THP ×4, ddAC ×4 → THP ×4. Primary endpoint: pCR (ypT0/is ypN0).

Results (data cut-off 12 Mar 2025)

• pCR: 67.3% vs 56.3% (Δ 11.2%, 95% CI 4.0–18.3; p=0.003). T-DXd alone 43.0%.
• HR+: 61.4% vs 52.3%. HR−: 83.1% vs 67.1%.
• RCB 0/I: 81.3% vs 69.1%.
• EFS: HR 0.56 (0.26–1.17), 4.5% maturity — not interpretable yet.
• Grade ≥3 AEs 37.5% vs 55.8%; serious AEs 10.6% vs 20.2%; LV dysfunction 1.3% vs 6.1% (Ann Oncol); adjudicated ILD 4.4% vs 5.1%.

Interpretation

• First anthracycline-free regimen to beat ddAC-THP for pCR in a phase 3 trial of high-risk disease.
• Caveats: open label; pCR is a surrogate; EFS/OS awaited; ILD needs vigilance.
• Adjuvant pathway unchanged: residual disease → T-DM1 (KATHERINE); pCR → complete HP.

For high-risk patients with cardiac concerns, T-DXd → THP is attractive where affordable. I would wait for EFS before abandoning anthracycline regimens universally.

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

Phase 3, open-label; n=557; untreated advanced EGFR ex19del/L858R NSCLC. Osimertinib 80 mg + pemetrexed + cisplatin/carboplatin ×4, then osimertinib + pemetrexed maintenance vs osimertinib alone.

Results

• PFS (primary, NEJM 2023): 25.5 vs 16.7 mo; HR 0.62.
• OS (final, ESMO 2025/NEJM): 47.5 vs 37.6 mo; HR 0.77 (95% CI 0.61–0.96; p=0.02); 57% maturity.
• OS at 36 mo: 63% vs 51%; at 48 mo: 49% vs 41%.
• CNS metastases at baseline: 36-mo OS 57% vs 40%.
• Grade ≥3 AEs (all causes): 70% vs 34% — mainly haematological, chemotherapy-related.

Where it fits (Oct 2026)

NCCN/ESMO list three preferred first-line options for common EGFR mutations: osimertinib, osimertinib + chemotherapy (FLAURA2) and amivantamab + lazertinib (MARIPOSA, also with OS benefit vs osimertinib). Choice depends on toxicity tolerance, logistics (IV vs oral), and disease features.

I favour FLAURA2 for fit patients with brain metastases or high tumour burden; osimertinib monotherapy remains entirely reasonable for elderly/frail patients or those prioritising fewer hospital visits.

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

• Desmoid tumours (aggressive fibromatosis): locally aggressive, non-metastasising; driven by Wnt/β-catenin (CTNNB1 or APC/FAP).
• Global consensus: active surveillance first; treat only progressive or symptomatic disease. Surgery is no longer default.
• Pre-DeFi systemic options: sorafenib (phase 3, Gounder NEJM 2018), low-dose methotrexate–vinblastine, NSAIDs/tamoxifen (weak evidence), doxorubicin-based chemotherapy.

Trial design

Phase 3, double-blind; n=142 with progressing desmoids (≥20% growth within 12 months). Nirogacestat 150 mg twice daily vs placebo. Primary endpoint: PFS.

Results

• PFS: HR 0.29 (95% CI 0.15–0.55; p<0.001).
• 2-year event-free probability: 76% vs 44%.
• ORR 41% vs 8%; complete response 7% vs 0%.
• Improvements in pain, desmoid-specific symptoms and quality of life.

Safety

Diarrhoea (most common), nausea, fatigue, hypophosphataemia, maculopapular rash. Ovarian dysfunction in ~75% of women of reproductive potential — mostly reversible, but counsel on fertility and contraception. Mostly grade 1–2.

Place in therapy

NCCN lists nirogacestat as a preferred systemic option for progressive/symptomatic desmoids. Longer follow-up and the optimal duration of therapy remain open questions.

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

Explore cancer history, treatments, and latest research.

Key first-line evidence

• EV-302 (n=886): EV + pembrolizumab vs gemcitabine + platinum. PFS 12.5 vs 6.3 mo (HR 0.45); OS 31.5 vs 16.1 mo (HR 0.47); ORR 67.7% vs 44.4%. Benefit regardless of cisplatin eligibility and PD-L1.
• CheckMate-901 (cisplatin-eligible): nivolumab + gem-cis vs gem-cis. OS 21.7 vs 18.9 mo (HR 0.78); PFS 7.9 vs 7.6 mo (HR 0.72); CR 21.7% vs 11.8%.
• JAVELIN Bladder 100: avelumab maintenance after response/stable disease on platinum. OS 21.4 vs 14.3 mo (HR 0.69).

Toxicity to anticipate with EV-pembro

Skin reactions (SJS/TEN rare but serious), peripheral neuropathy, hyperglycaemia, ocular surface toxicity, plus immune-related AEs. Check HbA1c and baseline neuropathy.

Later lines

• FGFR2/3 alteration: erdafitinib (THOR: OS 12.1 vs 7.8 mo vs chemo).
• Sacituzumab govitecan: US accelerated indication was withdrawn in 2024 after the confirmatory TROPiCS-04 trial did not improve OS.
• HER2-expressing tumours: trastuzumab deruxtecan has a US tumour-agnostic accelerated approval (HER2 IHC 3+).

The original oncosphere.in article was image-based and could not be recovered; this is a rewritten, referenced version under the same title.

Step 1 — Define the disease

• Histology confirmed on adequate tissue (core > FNA). Save blocks for molecular tests.
• Stage with appropriate imaging; confirm “advanced” really means incurable (oligometastatic disease may merit local therapy).
• Fitness: ECOG PS, organ function, comorbidities, patient goals.

Step 2 — Biomarkers before first line

| Tumour | Minimum biomarkers (NCCN/ESMO) | |—|—| | NSCLC (non-squamous) | EGFR, ALK, ROS1, BRAF, KRAS G12C, MET ex14, RET, NTRK, HER2; PD-L1 — broad NGS preferred | | Breast | ER/PR, HER2 (incl. HER2-low), germline BRCA; PIK3CA/ESR1 at relevant lines | | Colorectal | RAS, BRAF V600E, MMR/MSI, HER2 | | Gastric / GEJ | HER2, MMR/MSI, PD-L1 CPS, Claudin 18.2 | | Urothelial | FGFR2/3; (PD-L1 rarely decisive now) | | Any solid tumour | MMR/MSI, TMB, NTRK — tissue-agnostic options |

Step 3 — Match the therapy

• Driver-positive → targeted therapy first (e.g. osimertinib ± chemotherapy in EGFR-mutant NSCLC; alectinib/lorlatinib in ALK).
• Driver-negative, immunogenic → checkpoint inhibitor ± chemotherapy (NSCLC, gastric, oesophageal, urothelial, HNSCC, cervix, endometrial dMMR, TNBC PD-L1+).
• Target-defined ADCs → now first line in some settings (enfortumab vedotin + pembrolizumab in urothelial cancer).
• Chemotherapy remains the backbone for many, and alone when IO/targeted options are unavailable.

Step 4 — Practicalities

• Check drug access, insurance (CMCHIS, PM-JAY) and travel burden before promising a regimen.
• Baseline TSH, cortisol, LFTs before immunotherapy; LVEF before anti-HER2; ophthalmic/ILD counselling with relevant ADCs.
• Discuss palliative care early — improves quality of life and, in one RCT, survival (Temel, NEJM 2010).