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Sugar-sweetened beverages and risk of liver cancer (September 2023)
There is interest in evaluating the impact of sugar-sweetened beverages (such as regular sodas and fruit drinks) on the risk of developing liver cancer. In an observational study of almost 99,000 postmenopausal females, higher intake of sugar-sweetened beverages (one or more servings per day) was associated with an increased risk of developing liver cancer (hazard ratio 1.85) relative to less frequent consumption (three or less servings per month).1 These findings support the importance of limiting or avoiding sugar-sweetened beverages as part of a healthy diet for adults and for cancer prevention.
Lenvatinib plus pembrolizumab for advanced non-clear cell renal carcinoma (October 2023)
Advanced non-clear cell renal cell carcinoma (RCC) is rare, and there are limited data on the optimal approach to initial therapy. In a phase II trial in over 150 patients with advanced, systemic, therapy-naive non-clear cell RCC, objective responses for lenvatinib plus pembrolizumab by histology were 67 percent for those with translocation RCC, 54 percent for those with papillary RCC, 52 percent for those with unclassified RCC, and 28 percent for those with chromophobe RCC.2 We suggest lenvatinib plus pembrolizumab as initial therapy for patients with translocation RCC, and we consider this combination as one of several appropriate initial options for the other histologies.
Overall survival with adjuvant atezolizumab in resected non-small cell lung cancer (October 2023)
Longer-term overall survival (OS) data are emerging for adjuvant immune checkpoint inhibitors in resected non-small cell lung cancer (NSCLC). In a previously reported randomized trial in 882 patients with stage II to III NSCLC who had undergone surgery and adjuvant cisplatin-based chemotherapy, adjuvant atezolizumab resulted in OS hazard ratios of 0.95 overall, 0.71 among those with programmed death-ligand 1 (PD-L1) tumor cell (TC) >=1 percent, and 0.43 among those with PD-L1 TC >=50 percent.3 OS results remain immature. Based on results from this trial, atezolizumab is approved by the US Food and Drug administration (FDA) as adjuvant treatment following resection and platinum-based chemotherapy for stage II to III NSCLC whose tumors have PD-L1 TC >=1 percent, as determined by an FDA-approved test.4
BRAF/MEK targeted therapy in pediatric low-grade glioma (September 2023)
Targeted therapy is preferred for many children with BRAF V600E-mutant low-grade gliomas who require treatment beyond surgery. In a randomized, open-label, phase 2 trial in 110 such children requiring treatment after surgery for either symptoms or progression, first-line targeted BRAF/MEK inhibition (dabrafenib plus trametinib) improved overall response rate compared with carboplatin plus vincristine chemotherapy (47 versus 11 percent); it also improved median progression-free survival (20.1 versus 7.4 months) and was better tolerated.5 Overall survival data are not yet mature. Although not compared with radiation therapy, targeted therapy has the advantage of avoiding or at least delaying the long-term neurologic and cognitive consequences of radiation, which are of particular concern in younger patients.
Divarasib in G12C KRAS-mutant solid tumors (September 2023)
Novel agents are under investigation for G12C KRAS-mutant solid tumors. In a phase I study in 137 patients with advanced KRAS-mutant cancers, among the 60 patients with non-small cell lung cancer, the objective response rate to the covalent KRAS G12C inhibitor divarasib was 53 percent, with a median progression-free survival (PFS) of 13.1 months; among the subgroup of 55 patients with metastatic colorectal cancer, the response rate was 29 percent, with a median PFS of 6 months.6 Responses were also observed in patients with other solid tumors. Treatment was generally well tolerated, with grade >=3 events occurring in 12 percent of patients. We await further data and/or regulatory approval prior to use of divarasib in G12C KRAS-mutant solid tumors.
1. Zhao L, Zhang X, Coday M, et al. Sugar-Sweetened and Artificially Sweetened Beverages and Risk of Liver Cancer and Chronic Liver Disease Mortality. JAMA. 2023;330(6):537.
2. Albiges L, Gurney H, Atduev V, et al. Pembrolizumab plus lenvatinib as first-line therapy for advanced non-clear-cell renal cell carcinoma (KEYNOTE-B61): a single-arm, multicentre, phase 2 trial. Lancet Oncol. 2023;24(8):881. Epub 2023 Jul 11.
3. Felip E, Altorki N, Zhou C, et al. Overall survival with adjuvant atezolizumab after chemotherapy in resected stage II-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase III trial. Ann Oncol. 2023;34(10):907. Epub 2023 Jul 17.
4. Atezolizumab injection. United States Prescribing Information. US National Library of Medicine. https://www.accessdata.fda.gov/drugsatfda_docs/label/2021/761034Orig1s042lbl.pdf (Accessed on October 27, 2021).
5. Bouffet E, Hansford JR, GarreML, Hara J, et al. Dabrafenib plus Trametinib in Pediatric Glioma with BRAF V600 Mutations. N Engl J Med. 2023;389(12):1108.
6. Sacher A, LoRusso P, Patel MR, et al. Single-Agent Divarasib (GDC-6036) in Solid Tumors with a KRAS G12C Mutation. N Engl J Med. 2023;389(8):710.
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