Kyle Doherty

Key Takeaways Frontline intensification in TP53-comutated EGFR L858R disease gains support from TOP, FLAURA2, and MARIPOSA, showing meaningful PFS benefit versus osimertinib, with OS signals still immature. Case-based consensus favored combination systemic therapy for symptomatic bilateral brain metastases, with regimen selection split between osimertinib–platinum/pemetrexed and amivantamab–lazertinib. Post-progression sequencing after FLAURA2-like therapy includes platinum–pemetrexed rechallenge (when pemetrexed-free interval is prolonged), dato-DXd, or amivantamab plus chemotherapy, influenced by CNS stability. ADC enthusiasm remains divided given toxicity resembling or exceeding chemotherapy and uncertain target relevance post-EGFR, while overlapping deruxtecan payloads can restrict subsequent ADC trial access. Practical unmet needs include minimizing “time toxicity,” improving routine repeat biopsy at progression to capture actionable resistance (e.g., BRAF fusions), and establishing predictive biomarkers to guide regimen choice and ADC sequencing. SHOW MORE

Key Takeaways KRYSTAL-10 randomized 461 patients (ECOG 0–1) to adagrasib 600 mg BID plus cetuximab q2w versus FOLFIRI or mFOLFOX ± VEGF/VEGFR inhibitor, with OS and BICR-assessed PFS as dual primaries. Overall survival was not significantly improved (HR 0.83; P=.0938), with near-identical medians (~21.6–21.7 months) and modestly higher late OS rates in the targeted-therapy arm. Progression-free survival also missed significance (HR 0.89; P=.3241), with medians of 7.5 months for adagrasib/cetuximab versus 8.1 months for chemotherapy. Objective response strongly favored adagrasib/cetuximab (47% vs 16%), including higher CR frequency (7% vs <1%), while median DOR was similar (~9.2 vs 9.4 months). Post-progression therapy likely confounded survival, as subsequent KRAS G12C inhibitor use was higher after chemotherapy (30% vs 4%), alongside expected toxicity tradeoffs (GI/skin vs hematologic). SHOW MORE

OncLive spoke with expert investigators to gather insights on the role of AI in cancer care, including oncologic surgery and drug development.

Key Takeaways ATOMIC randomized patients to 6 months mFOLFOX6 ± atezolizumab, followed by 6 months atezolizumab maintenance in the combination arm, after curative resection for stage III dMMR disease. Landmark methodology at 12 cycles (6 months) assessed DFS among patients alive and progression-free, using log-rank testing and Cox models adjusted for T and N stage. Benefit from adding atezolizumab was pronounced with >6 FOLFOX cycles (adjusted HR 0.45) and absent with ≤6 cycles (adjusted HR 0.84), suggesting duration-dependent interaction. Atezolizumab exposure ≥12 cycles (combination plus monotherapy) was associated with improved DFS versus FOLFOX alone (adjusted HR 0.48), while <12 cycles showed a nonsignificant trend. Per-cycle modeling suggested incremental DFS benefit per additional FOLFOX cycle only in the combination arm (HR 0.93/cycle), alongside higher post-FOLFOX atezolizumab continuation rates. SHOW MORE

Key Takeaways Phase 1 part 1B required CCNE1 amplification or central cyclin E1 overexpression and ECOG 0–1; TEAEs were common, grade ≥3 events occurred in 35.6%, and no fatal TEAEs occurred. At 100 mg daily (n=14), ORR was 35.7% with all partial responses, DCR 71.4%, median DOR 3.6 months, and median PFS 4.5 months. Across 50/100 mg (n=30), ORR was 33.3% and median PFS 5.3 months; responses occurred with CCNE1 amplification and with cyclin E1 overexpression absent amplification. MAESTRA 2 randomizes 466 patients 1:1 to INCB123667 50 mg BID versus weekly paclitaxel, PLD, gemcitabine, or topotecan, requiring cyclin E1 IHC overexpression and prior bevacizumab. Development strategy anticipates combinations, including potential activity in CDK4/6-resistant settings and rational pairing with PD-(L)1 or PARP inhibitors, emphasizing oral maintenance feasibility. SHOW MORE

Key Takeaways ELEVATE randomized completely resected stage IB–IIIB ALK-positive NSCLC to ensartinib 225 mg daily versus placebo for up to 24 months after any planned adjuvant chemotherapy. At 24 months, stage II–IIIB DFS favored ensartinib (86.4% vs 53.5%; HR 0.20; 95% CI 0.11–0.38; P<.001). Across the full stage IB–IIIB cohort, 24-month DFS was 87.3% with ensartinib and 57.2% with placebo (HR 0.20; 95% CI 0.10–0.37). Safety showed 98.5% any-grade AEs and 35.8% grade ≥3 AEs with ensartinib, versus 92.0% and 18.2% on placebo; treatment-related fatal AEs were not observed. SHOW MORE

Key Takeaways COMRADE randomized mCRPC patients with ≥2 bone metastases, no visceral disease, ECOG 0–1, and no prior PARP inhibitor or radium-223 exposure, allowing prior mCRPC therapies. Participants received olaparib 200 mg twice daily continuously plus radium-223 55 kBq/kg every 4 weeks for ≤6 cycles versus radium-223 alone, stratified by docetaxel and bone burden. FACT-P change did not differ significantly between arms at week 12 (−4.87) or week 24 (1.79), indicating no clear quality-of-life detriment from combination therapy. BPI pain severity was similarly nonsignificant at week 12 (0.44) and week 24 (−0.20), with comparable clinically meaningful worsening of pain and interference by 24 weeks. Questionnaire completion declined over time (FACT-P week 24: 44% combination, 56% control), underscoring the need for adequately powered, prospective PRO capture in evolving radiopharmaceutical combinations. SHOW MORE

Key Takeaways FDA authorized perioperative pembrolizumab (or pembrolizumab/berahyaluronidase) plus enfortumab vedotin for adult muscle-invasive bladder cancer treated with cystectomy. KEYNOTE-B15/EV-304 showed median event-free survival was not reached with pembrolizumab/enfortumab vedotin versus 48.5 months with gemcitabine/cisplatin. Risk of events was reduced versus chemotherapy (HR, 0.53; 95% CI, 0.41-0.70; P < .0001), supporting a clinically meaningful perioperative benefit. Overall survival data were immature, with median OS not reached in either arm, though favoring pembrolizumab/enfortumab vedotin (HR, 0.65; P = .0029). SHOW MORE

Updated Data From PrTK03 in Prostate Cancer: Key Takeaways Updated phase 3 PrTK03 data showed that aglatimagene besadenovec plus valacyclovir

Key Takeaways Penpulimab achieved a significant DFS benefit versus surveillance (HR 0.37; 95% CI, 0.16–0.89), with higher 1-year (94.25% vs 80.46%) and 2-year DFS (88.68% vs 75.38%). Treatment consisted of penpulimab 200 mg IV every 3 weeks for up to 17 cycles post-nephrectomy in adults with very high-risk ccRCC, ECOG 0–1, and no prior systemic therapy. Prespecified subgroup analyses showed generally consistent DFS improvement across older age, ECOG 0, M0 status, very-high risk T3 disease, and radical nephrectomy cohorts. Safety was manageable: 49.4% had any TRAE, 6.9% had grade 3–4 TRAEs, and common events included rash, proteinuria, pruritus, thyroid dysfunction, and fatigue. Progression correlated with suppressed antitumor immune plasma proteins, depletion of immunostimulatory microbiota-associated metabolites, metabolic reprogramming signatures, and candidate plasma biomarkers linked to relapse risk. SHOW MORE