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Ribociclib in advanced breast cancer (March 2022)
The addition of the cyclin-dependent kinase (CDK) 4/6 inhibitor ribociclib to letrozole was previously shown in a randomized trial to improve progression-free survival in postmenopausal patients with hormone receptor (HR)-positive, HER2-negative, treatment-naive, advanced breast cancer. Now, in longer follow-up of 6.6 years, the addition of ribociclib also resulted in improved overall survival (median 64 versus 51 months) [1]. Based on these and other data, we continue to recommend the addition of a CDK 4/6 inhibitor to an aromatase inhibitor as initial therapy for most patients with HR-positive, HER2-negative, advanced breast cancer, also incorporating ovarian suppression for premenopausal patients.
Updated ASCO guideline for adjuvant therapy in stage II colon cancer (March 2022)
Updated guidelines for adjuvant therapy in stage II colon cancer from the American Society for Clinical Oncology (ASCO) are available [2]. The guidelines recommend against routine use of adjuvant chemotherapy, especially for individuals at low risk of recurrence, reiterating the conclusion from 2004 that a significant subgroup of patients with stage II colon cancer are not expected to benefit from such therapy. Although expert groups vary in how they define high-risk stage II disease, ASCO and others recommend offering chemotherapy to patients who are at increased risk for recurrence. We suggest selecting patients with chemotherapy based on clinicopathologic risk factors and DNA mismatch-repair status.
Long-term survival with nivolumab plus ipilimumab in advanced renal cell carcinoma with sarcomatoid features (March 2022)
For patients with advanced renal cell carcinoma (RCC) with sarcomatoid features, immunotherapy is more effective than vascular endothelial growth factor receptor (VEGFR) inhibitors, but long-term overall survival (OS) data were previously limited. In extended follow-up of a phase III trial in over 100 patients with treatment-naive intermediate- or poor-risk advanced RCC with sarcomatoid features, nivolumab plus ipilimumab improved five-year OS compared with sunitinib (47 versus 21 percent) [3]. Based on these data, for patients with advanced or metastatic RCC with sarcomatoid features, we continue to recommend initial therapy with nivolumab plus ipilimumab rather than VEGFR inhibitors.
Tebentafusp for metastatic uveal melanoma (March 2022)
Metastatic uveal melanoma is a rare, aggressive malignancy with few effective treatment options. Tebentafusp is a bispecific T cell engager targeting glycoprotein 100, a uveal melanoma antigen. In a phase III trial in almost 400 patients with positive human leukocyte antigen (HLA)-A*02:01 and systemic treatment-naive, advanced uveal melanoma, tebentafusp improved one-year overall survival rates compared with investigator's choice of immunotherapy or chemotherapy (73 versus 59 percent) [4]. Based on these data, the US Food and Drug Administration approved tebentafusp for adults with advanced unresectable or metastatic uveal melanoma who are HLA-1*02:01 positive [5], and we recommend its use as initial therapy in this patient population.
Survival benefit with ALK inhibitors over chemotherapy in ALK-positive NSCLC (March 2022)
Advanced non-small cell lung cancers (NSCLC) that harbor activating ALK genetic alterations are sensitive to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors, which have previously shown progression-free survival benefits over chemotherapy. A meta-analysis of six trials in patients with advanced ALK-positive NSCLC found that ALK inhibitors also improved overall survival compared with chemotherapy (hazard ratio 0.84), despite substantial cross-over from chemotherapy to ALK inhibitors after the study period [6]. Moreover, ALK inhibitors increased health-related quality-of-life measures. These data reinforce our approach of using an ALK inhibitor as initial therapy for patients with advanced ALK-positive NSCLC.
1. Hortobagyi GN, Stemmer SM, Burris HA, et al. Overall Survival with Ribociclib plus Letrozole in Advanced Breast Cancer. N Engl J Med. 2022;386(10):942.
2. Baxter NN, Kennedy EB, Bergsland E, et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update. J Clin Oncol. 2022;40(8):892. Epub 2021 Dec 22.
3. Tannir NM, Signoretti S, Choueiri TK, et al. Efficacy and safety of nivolumab plus ipilimumab (N+I) versus sunitinib (S) for first-line treatment of patients with advanced sarcomatoid renal cell carcinoma (sRCC) in the phase 3 CheckMate 214 trial with extended 5-year minimum follow-up. J Clin Oncol. 2022;40;6S.
4. Nathan P, Hassel JC, Rutkowski P, et al. Overall Survival Benefit with Tebentafusp in Metastatic Uveal Melanoma. N Engl J Med. 2021;385(13):1196.
5. Tebentafusp: US Food and Drug Administration Prescribing Label https://www.accessdata.fda.gov/drugsatfda_docs/label/2022/761228s000lbl.pdf (Accessed on January 31, 2022).
6. Cameron LB, Hitchen N, Chandran E, et al. Targeted therapy for advanced anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer. Cochrane Database Syst Rev. 2022;1:CD013453. Epub 2022 Jan 7.
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