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Nivolumab plus Gemcitabine–Cisplatin in Advanced Urothelial Carcinoma

For metastatic urothelial carcinoma, the combination of nivolumab + gemcitabine (gem) /cisplatin (cis) resulted in an improved overall response rate (ORR) of 58 vs. 43%, progression-free survival (PFS) at 12 months of 34 vs. 22% and higher rates of complete response (CR) at 22 vs. 12%. This is the first study to improve upon the chemotherapy doublet of gem/cis in this disease setting. While an interesting treatment option, this has not yet made it into the NCCN guidelines and pembrolizumab + enfortumab seems to be a better tolerated, non-chemo option that is gaining traction.

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Osimertinib with or without Chemotherapy in EGFR-Mutated Advanced NSCLC

Osimertinib with chemotherapy improved the chance of being alive at two years compared to targeted therapy alone at 57 vs 41%. Further analysis of FLAURA2 and new studies will surely look to identify which patients benefit most from the combination of targeted therapy and chemotherapy. For young or healthy patients, this is an acceptable first line option. This is not yet reflected on NCCN but is likely to be added soon.

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Amivantamab plus Chemotherapy in NSCLC with EGFR Exon 20 Insertions

Phase III study of amivantamab + chemotherapy vs. chemotherapy alone as first-line therapy in patients with Exon-20 EGFR mutations. While the results of this study are impressive, one wonders what the results would be if the comparator arm were a targeted option. This is not yet reflected in the NCCN guidelines but likely will be added.

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Nimotuzumab Plus Gemcitabine for K-Ras Wild-Type Locally Advanced or Metastatic Pancreatic Cancer

Asian study of nimotuzumab (humanized EGFR-inhibitor) + gemcitabine (gem) vs. gem alone. The overall survival (OS) was 10.9 vs. 8.5 months in favor of the combination arm. While the OS difference is small, recall that the OS in the NALIRIFOX and FOLFIRINOX studies are similar. The safety profile of nimotuzumab + gemcitabine is superior to a triplet or double cytotoxic chemotherapy combination regimen. This drug is currently not available in the USA but is approved for nasopharyngeal carcinoma in China.

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Zanubrutinib Versus Ibrutinib in Symptomatic Waldenström Macroglobulinemia: Final Analysis From the Randomized Phase III ASPEN Study

Final results from the ASPEN study confirm the strong long-term superiority of zanubrutinib over ibrutinib in symptomatic WM. While overall survival (OS) and progression-free survival (PFS) end-points are still to be reached, demonstrating the good prognosis of this disease, toxicities and response rates are much better with zanubrutinib. This is a cat-1 indication oof NCCN and a compelling option for use in this population.

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Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994

In the EORTC-55994 study, neoadjuvant chemotherapy followed by chemoradiation + surgery was not superior to chemoradiation for patients with stage IB2 – IIB cervical cancer. However, the toxicity was acceptable, so for patients with more locally advanced disease, it could be considered. Regardless, the SOC will remain concurrent chemotherapy and radiation for these patients.

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