The Targeted Pulse: Adagrasib Bests Docetaxel in Pretreated KRAS G12C-NSCLC, Adding Nivolumab to Tivozanib Yields No benefit in RCC, and More

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Adagrasib Comes Out on Top in Pretreated KRAS G12C-NSCLC Vs Docetaxel

Adagrasib (Krazati) demonstrated significantly better results than docetaxel for patients with previously treated KRAS G12C-mutated non–small cell lung cancer (NSCLC) even in those with existing brain metastases. These findings from the phase 3 KRYSTAL-12 trial (NCT04685135), presented at the 2024 ESMO Congress, evaluated 453 patients who had previously received treatment with platinum-based chemotherapy and anti–PD-(L)1 therapy.

“Adagrasib demonstrated an improved intracranial efficacy compared with docetaxel in patients with treated, neurologically stable baseline brain metastases. Systemic overall response rate, duration of response, and progression-free survival were numerically greater with adagrasib than with docetaxel, regardless of the presence of brain metastases. The safety profiles of adagrasib and docetaxel were comparable in both patients with and without brain metastases and were consistent with all randomized patients.” Fabrice Barlesi, MD, PhD, said during a presentation of the findings. Barlesi is a thoracic oncologist at the Paris Saclay University and chief executive officer of Gustave Roussy Institute, in France.

TiNivo-2 Study Finds No Benefit Adding Nivolumab to Tivozanib in Metastatic RCC

Data from the phase 3 TiNivo-2 study (NCT04987203) indicate that adding nivolumab (Opdivo) to tivozanib (Fotivda) did not result in improved clinical outcomes. The study included patients with metastatic renal cell carcinoma (RCC) who had progressed on or after treatment with a PD-(L)1 inhibitor. During the presentation at ESMO 2024, Toni Choueiri, MD, emphasized the uncertainties regarding the optimal treatment sequence for patients with RCC who have progressed after an immune checkpoint inhibitor (ICI) therapy. He questioned whether rechallenging with the same or a different ICI would improve outcomes, and whether using a non-ICI drug before rechallenging or taking a break from ICIs could affect the results.

“TiNivo-2 was the first phase 3 trial to evaluate the efficacy and safety of a PD-1 inhibitor after progression on or following treatment with a PD-[L]1 therapy,” said Choueiri, of Dana-Farber Cancer Institute in Boston Massachusetts, during a presentation. “TiNivo-2 is a negative study, but I strongly believe it’s important. It is practice changing, and it should make us think twice now…These results support tivozanib monotherapy at 1.34 kg as a second-line therapy option for patients who have progressed on previous immune checkpoint inhibitor (ICI) therapy.”

T-DXd Performs in HER2+ Breast Cancer With Brain Metastases

Fam-trastuzumab deruxtecan-nxki (T-DXd; Enhertu) demonstrated durable overall and intracranial activity in patients with HER2-positive metastatic breast cancer including those with stable and active brain metastases, according to data from the phase 3b/4 DESTINY-Breast12 study (NCT04739761). Approximately half of patients with HER2-positive metastatic breast cancer develop brain metastases, Nancy U. Lin, MD, stated during a presentation of the data at ESMO 2024.

“…The safety profile of T-DXd was consistent with previous reports, and no new safety signals were identified. Interstitial lung disease/pneumonitis remains a significant safety risk of T-DXd especially for patients with brain metastases who are on concomitant steroids. Careful attention to pneumocystis pneumonia prophylaxis and workup for opportunistic infections is warranted,” said Lin, from the Department of Medical Oncology at Dana-Farber Cancer Institute.

What The Newly Approved Subcutaneous Atezolizumab Means for NSCLC, SCLC

The subcutaneous formulation of atezolizumab and hyaluronidase-tqjs (Tecentriq Hybreza) has been approved by the FDA based on data from the open-label, multicenter, international IMscin001 (NCT03735121) trial. The approval covers all adult indications for the intravenous (IV) version of the agent, including NSCLC, small cell lung cancer, hepatocellular carcinoma, melanoma, and alveolar soft part sarcoma. In the trial, 371 patients with locally advanced or metastatic NSCLC were randomly assigned in a 2:1 ratio to receive either subcutaneous or IV atezolizumab until disease progression or unacceptable toxicity occurred.

“As the active ingredient of atezolizumab is identical in both the subcutaneous and IV formulations, it is expected that noninferior systemic exposure would result in a comparable degree of target-site saturation, and thus similar efficacy for both routes of administration. This is supported by the early efficacy and safety findings in this study, which show similar clinical outcomes between the treatment arms,” authors wrote in the study published in the Annals of Oncology.

Refining Individualized HER2+ Breast Cancer Treatments with Latest Advances

In this article, Naomi Dempsey, MD, discussed less toxic and more personalized regimens for patients with HER2+ breast cancer. She highlighted new data from multiple trials, including the APT (NCT00542451), ATEMPT (NCT01853748), and TRAIN-2 (NCT01996267) trials, as well as ongoing trials, to provide a comprehensive view of the various data and how to implement it into clinical practice for individual patients.

“The TRAIN-3 trial [NCT03820063] evaluated patients with HER2+ breast cancer receiving neoadjuvant chemotherapy using an MRI-directed approach to determine whether chemotherapy could be ended early. I think this is an interesting approach, particularly for patients who may not tolerate it well…I think there are a number of approaches there that maybe are not what we do in a usual clinical situation, but where we could consider something like adding [trastuzumab] and pertuzumab to an aromatase inhibitor for patients who are triple positive,” said Dempsey, breast medical oncologist at Baptist Health Miami Cancer Institute, in the interview with Targeted OncologyTM

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