ASCO Spotlight With Joel Neal, MD, PhD: Says Cabozantinib/Atezolizumab May Fulfill Unmet Need in NSCLC

For patients with non–small cell lung cancer (NSCLC) and no option of a targeted treatment due to genetic alteration, cabozantinib plus atezolizumab could become a second-line treatment beyond chemotherapy, noted Joel Neal, MD, PhD, an associate professor in the Division of Oncology at Stanford Cancer Institute in California.

Neal, lead investigator on the COSMIC-021 trial (NCT03170960), spoke with Evidence-Based Oncology™ (EBO) about the updated analyses presented at the 2022 annual meeting of the American Society of Clinical Oncology (ASCO).

EBO: What do the phase 1b results from COSMIC-021 show in NSCLC?

Neal: The COSMIC-021 phase 1b study included a number of different cohorts across a number of different types of tumors, as well as a number of different patients with NSCLC. One of the most interesting cohorts in my opinion was cohort 7, in which patients who had had prior immune checkpoint inhibitor therapy, plus or minus optional platinum chemotherapy, then went on at time of tumor progression to get second-line treatment with cabozantinib plus atezolizumab.

We reported at ASCO a couple of years ago that the first 30 patients had a significant response rate, higher than we would have seen otherwise, in the 20% range. We would have expected cabozantinib or chemotherapy alone to [have] more like less than 10% response rates. So based on that, in this phase 1b we expanded that cabozantinib cohort to include 81 patients and started [randomly assigning] them in the middle between the cabozantinib-plus-atezolizumab cohort and a cabozantinib-alone cohort to try and get a sense of how cabozantinib [was] performing alone after prior immunotherapy in the frontline setting, as well as together with continued immunotherapy.

EBO: What unmet need in NSCLC is potentially addressed through treatment with cabozantinib plus atezolizumab?

Neal: From here, we’re excited that cabozantinib plus atezolizumab might have a role in the second-line treatment of NSCLC. Docetaxel alone is the approved therapy, but often providers use other single-agent chemotherapies relatively interchangeably—of course with the exception of patients with tumors harboring targeted alterations like EGFR, ALK, and all the other molecular alterations we have.

So for those patients without a targetable therapy, [we are] encouraged that the second-line treatment using this VEGF small molecule inhibitor plus immunotherapy, a strategy that’s been successful in renal cell cancer and is emerging in other cancers, may meet this unmet need of something other than chemotherapy to offer [patients] in the second-line setting. To establish that, we’re still running a phase 2 clinical trial (NCT04310007), which has 3 arms of cabozantinib/nivolumab, cabozantinib alone, and [investigator’s] choice of single-agent chemotherapy. That’s the ECOG-ACRIN EA5191 study. And then there’s also a phase 3 study being run, the CONTACT-01 study (NCT04471428), which has finished accrual, which is [evaluating] cabozantinib and atezolizumab vs docetaxel.

So as we present these data, it’s very exciting to actually say that the phase 3 is already done and we’re awaiting the results. Hopefully that could be practice changing soon. 

Reference
Neal JW, Santoro A, Viteri S, et al. Cabozantinib (C) plus atezolizumab (A) or C alone in patients (pts) with advanced non–small cell lung cancer (aNSCLC) previously treated with an immune checkpoint inhibitor (ICI): results from cohorts 7 and 20 of the COSMIC-021 study. J Clin Oncol. 2022;40(suppl 16):9005. doi:10.1200/JCO.2022.40.16_supp.9005