The Targeted Pulse: Recent Approvals in Breast and Colorectal Cancers and the Controversy Over Adjuvant CDK4/6 Inhibitors in Breast Cancer

Dato-DXd Wins an FDA Approval for HR+/HER2– Breast Cancer

Datopotamab deruxtecan (Dato-DXd) receives an FDA approval for treating unresectable or metastatic hormone receptor-positive (HR+), HER2-negative (HER2–) breast cancer that has been previously treated with systemic therapy. Findings from the phase 3 TROPION-Breast01 trial (NCT05104866) support the approval.

In the trial, Dato-DXd was compared with investigator’s choice of chemotherapy and demonstrated an improvement in overall survival vs chemotherapy in patients with inoperable or metastatic HR+, HER2– breast cancer who had received 1 or 2 prior lines of systemic therapy. For details on the TROPION-Breast01 trial data as well as the recommended dose and frequency, visit the full article here.

Sotorasib/Panitumumab Takes Home An Approval For KRAS G12C-Mutant CRC

The combination of sotorasib (Lumakras) and panitumumab (Vectibix) has received FDA approval for the treatment of previously treated KRAS G12C-mutated metastatic colorectal cancer. In the CodeBreaK 300 study (NCT05198934), presented at the 2023 ESMO Congress, sotorasib was evaluated at 2 different doses (960 mg and 240 mg). These doses were then compared with investigator’s choice of trifluridine and tipiracil (Lonsurf) or regorafenib (Stivarga).

Overall, both doses of sotorasib outperformed the investigator’s choice, with the higher dose (960 mg) demonstrating the greatest efficacy. For the breakdown of data from the CodeBreaK 300 study, read the full article here.

Adjuvant CDK4/6 Inhibitors Under Scrutiny in Breast Cancer

In this article, John M. Burke, MD, explains the controversy over adjuvant therapy with CDK4/6 inhibitors ribociclib (Kisqali), and abemaciclib (Verzenio) for HR+, HER2– breast cancer. Burke highlights 2 articles, 1 published in the 2023 Lancet Oncology and the other in the 2024 European Journal of Cancer, both of which explore data from the phase 3 monarchE trial (NCT03155997) and the phase 3 NATALEE trial (NCT03701334), respectively.

In addition to exploring the clinical data, Burke discusses the economic implications of using ribociclib, in addition to its efficacy data. “Based on NATALEE results, they estimated that 30 patients would need to be treated to prevent 1 invasive disease-free survival [iDFS] event. In addition, the authors calculated that with the cost of a 3-year course of ribociclib being approximately $550,000, the health care system would need to spend approximately $11 million to prevent 1 iDFS event,” Burke wrote in his article. Burke is hematologist and medical oncologist, Rocky Mountain Cancer Centers and associate chair, US Oncology Hematology Research Program, Aurora, CO. For the full scope of this interesting perspective, read Burke’s full article here.

Sabari Explains Data from the MARIPOSA trial for EGFR-mutated NSCLC

During a Case-Based Roundtable event, Joshua K. Sabari, MD, examines data from the MARIPOSA-1 trial (NCT04487080) and shares his key takeaways on subsequent therapies for EGFR-mutated non–small cell lung cancer (NSCLC). In the MARIPOSA-1 trial, amivantamab (Rybrevant) and lazertinib (Lazcluze) were compared with osimertinib (Tagrisso) for patients with treatment-naive, EGFR-mutated (Ex19del or L858R) locally advanced or metastatic NSCLC.

“Rash is a major issue with this therapy, and it is one of the more chronic toxicities. Both therapies [are probably responsible]; they both have EGFR inhibition, but amivantamab likely has more EGFR wild-type inhibition than lazertinib. Lazertinib was more EGFR mutant-specific. In my own experience, they complement each other, but I think most of the effect is driven by amivantamab,” Sabari said at the event. Sabari is assistant professor, Department of Medicine NYU Grossman School of Medicine and director, High Reliability Organization Initiatives at the Perlmutter Cancer Center, New York, New York. For the complete discussion on this regimen and information on navigating venous thrombotic events, read the full are here.

TAR-200 Is Under Real-Time FDA Review for BCG-Unresponsive High-Risk NMIBC

A new drug application for TAR-200, an intravesical drug system, is currently under review by the FDA to treat BCG-unresponsive high-risk non-muscle-invasive bladder cancer (HR-NMIBC) with carcinoma in situ (CIS). The indication applies to this disease, regardless of the presence of papillary tumors.

“Just as important as complete response rate, we want to know that this is also a durable treatment, meaning that patients, when they respond, tend to respond for a long period of time. We want to know how these patients are doing at 1 year, at 18 months, at 24 months, and so that is the next step. It is to show patients that this not only is an effective treatment, but it can be a long-term solution as well,” Joseph M. Jacob, MD, urological oncologist, Department of Urology, Upstate Medical University, Syracuse, New York, told Targeted Oncology^TM in an interview. For more details on TAR-200’s method of action, read the full article here.

Thank you for joining us for this week’s Targeted Pulse. Look out for more recaps to come.

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