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Bevacizumab and Erlotinib in Hereditary and Sporadic Papillary Kidney Cancer

There is no standard therapy for this type of cancer, which could be sporadic or associated with germline mutations (Hereditary leiomyomatosis and renal-cell cancer) in HLRCC-associated papillary renal-cell carcinoma. Responses were observed in 72%, the median progression-free survival was 21.1 months, and the median overall survival was 44.6 months. In sporadic papillary renal-cell carcinoma 35% had responded with a median progression-free survival of 8.9 months, median overall survival of 18.2 months. This is a promising combination.

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Nonoperative Management of Mismatch Repair—Deficient Tumors

Two cohorts, one for patients with colon cancer and the second for all other patients. Of the 103 patients who completed treatment across both cohorts, 84 had a clinical complete response and 82 did not undergo surgery. Among the 117 total patients, recurrence-free survival at two years was 92%. Only 20-months follow up for now. It will be interesting to see how this goes with future updates but seems promising.

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Chemotherapy-free neoadjuvant pembrolizumab combined with trastuzumab and pertuzumab in HER2-enriched early breast cancer (WSG-KEYRICHED-1): a single-arm, phase 2 trial

The WSG-KEYRICHED-1 phase II trial evaluated a chemotherapy-free neoadjuvant regimen of pembrolizumab plus trastuzumab and pertuzumab in HER2-enriched early breast cancer, achieving a pathological complete response (pCR) rate of 46.5% (95% CI 31.2–62.6%). No survival data (e.g., EFS or OS) were reported, but the regimen showed an acceptable safety profile with no new cardiac toxicity signals. The chemo-free approach suggests promising potential for de-escalation in this subtype, but we’ll need randomized trials to confirm its efficacy and safety.

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Neoadjuvant PD-1 and PD-L1 Blockade With Chemotherapy for Borderline Resectable and Unresectable Stage III Non–Small Cell Lung Cancer

The phase II trial of neoadjuvant PD-1/PD-L1 blockade plus chemotherapy in borderline resectable and unresectable stage III NSCLC showed a significant improvement in event-free survival (EFS) with the combination (24.1 vs 10.6 months) compared to chemotherapy alone, with a hazard ratio (HR) of 0.62. Major pathological response rates were higher with immunotherapy (44.7% vs 22.3%), and no new safety signals were noted. The regimen improved surgical resection rates (68% vs 52%) without increasing perioperative complications. This validates chemoIO in the neoadjuvant setting particularly in whom we wish to pursue resection or avoid chemoradiation. It would be great to see this compared to chemoradiation followed by immunotherapy rather than chemotherapy alone.

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Randomized Phase III Trial of Ramucirumab Beyond Progression Plus Irinotecan in Patients With Ramucirumab-Refractory Advanced Gastric Cancer: RINDBeRG Trial

The RINDBeRG phase III trial investigated Ram + IRI versus IRI alone in Ram-refractory advanced gastric cancer, showing a significant improvement in progression-free survival (PFS) (3.8 vs 2.8 months) but no significant difference in overall survival (OS) (9.4 vs 8.5 months). The combination therapy achieved a higher overall response rate (ORR) (22.1% vs 15.0%) and disease control rate (DCR) (64.4% vs 52.1%), indicating likely modest antitumor activity. This combo offers a slight edge in delaying progression, but the lack of overall survival (OS) benefit means we’ll need to carefully consider its role in practice.

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Acalabrutinib Plus Bendamustine-Rituximab in Untreated Mantle Cell Lymphoma

The ECHO phase III trial evaluated acalabrutinib + bendamustine-rituximab (BR) vs placebo plus BR in untreated mantle cell lymphoma (MCL) patients ineligible for transplant, showing a significant improvement in progression-free survival (PFS) (66.4 vs 49.6 months) with a hazard ratio (HR) of 0.73. The combination achieved a higher overall response rate (ORR) (91.0% vs 88.0%) and complete response (CR) rate (66.6% vs 53.5%), supporting its efficacy in this older population. Of note, side effects like pneumonia, atrial fibrillation, and infections were more frequent with acalabrutinib, with serious adverse effects in 69% versus 62% for placebo. This triplet regimen could redefine first-line treatment for our MCL patients, but we’ll need to stay vigilant about managing toxicities, especially in older patients.

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