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Dr Joel W. Neal: Cabozantinib/Atezolizumab May Fullfill Unmet Targeted Treatment Need in NSCLC


Joel W. Neal, MD, PhD, associate professor, Division of Oncology, Stanford Cancer Institute, is lead investigator on the COSMIC-021 trial, which is investigating cabozantinib plus atezolizumab vs cabozantinib alone in patients with advanced non–small cell lung cancer (NSCLC) as a possible second-line treatment beyond chemotherapy.

For patients with non–small cell lung cancer (NSCLC) who do not have the option of a targeted treatment because of their genetic alteration, cabozantinib plus atezolizumab could become a potential second-line treatment beyond chemotherapy, noted Joel Neal, MD, PhD, associate professor, Division of Oncology, Stanford Cancer Institute.

Neal is lead investigator on the COSMIC-021 trial, updated analyses of which were presented at this year’s American Society of Clinical Oncology (ASCO) Annual Meeting.


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

So the COSMIC-021 phase 1bstudy included a number of different cohorts across a number of different types of tumors, as well as a number of different patients with non–small cell lung cancer. 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 to at time of tumor progression 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 be 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 randomizing them in the middle between the cabozantinib-plus-atezolizumab cohort and a cabozantinib-alone cohort to try and get a sense of how is cabozantinib performing alone after prior immunotherapy in the frontline setting, as well as together with continued immunotherapy.

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

From here, we’re excited that cabozantinib plus atezolizumabmight have a role in the second-line treatment of non–small cell lung cancer [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 a bunch of other cancers, may meet this unmet need of something other than chemotherapy to offer in the second-line setting. To establish that, we’re still running a phase 2 clinical trial, which has 3 arms of cabozantinib/nivolumab, cabozantinib alone, and dealer’s choice of single-agent chemotherapy. That’s the ECOG-ACRIN EA 5191 study. And then there’s also a phase 3 study being run, the CONTACT-01 study, which has finished accrual, which is cabozantinib and atezolizumabvs docetaxel.

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

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