ONCAlert | Upfront Therapy for mRCC

Investigators Explore Neoadjuvant Immunotherapy in Hepatocellular Carcinoma

Arjun V. Balar, MD
Published Online: Nov 05,2019
Arjun V. Balar, MD
Arjun V. Balar, MD
In solid tumor oncology, an evolving treatment paradigm is getting more and more attention—and no, I’m not referring to immunotherapy. In localized solid tumors, surgery is often a standard of care, with intent being toward cure. However, for patients at high-risk of systemic relapse (eg, positive lymph nodes in someone who undergoes a partial colectomy with lymph node dissection for colon cancer), adjuvant therapy is often recommended to reduce the risk and improve rate of cure. The paradigm is now evolving toward neoadjuvant treatment (ie, before surgery). This has many advantages (and some disadvantages) to adjuvant treatment, and recent advances in systemic immunotherapy agents spurred renewed interest in this approach.

Historically, one of the biggest advantages to neoadjuvant therapy involved in vivo assessment of treatment effectiveness, which can then inform prognosis and subsequent therapy, if indicated. For example, in a patient with muscle-invasive bladder cancer who receives neoadjuvant chemotherapy prior to radical cystectomy, a complete pathologic response to neoadjuvant chemotherapy is associated with an 85% to 90% likelihood of cure. However, if residual muscle-invasive disease is present despite neoadjuvant chemotherapy, a patient is at higher risk of systemic relapse and should be counseled about clinical trials of experimental adjuvant treatment.

This era of immunotherapy brings even more reason to pursue neoadjuvant treatment. The immune microenvironment of a primary tumor contains immune cell populations that attempt to control the tumor; thus, it is optimal to administer a systemic immunotherapy agent, designed to proliferate and expand the tumor resident immune populations, before surgery rather than after, when those precious immune cells were resected along with the tumor. That’s the immunobiology equivalent of throwing the baby out with the bathwater.

The recent 13th Annual Conference of the International Liver Cancer Association featured presentations of several provocative trials of systemic immunotherapy agents and combinations in hepatocellular carcinoma (HCC), none more interesting than a preoperative study of short-course nivolumab (Opdivo) versus ipilimumab (Yervoy) plus nivolumab in patients with surgically resectable HCC. Surgery alone is the current standard of care but associated with a high risk of relapse. Interestingly, 29% of patients achieved a pathologic complete response to neoadjuvant immunotherapy, suggesting that this approach is not just feasible (ie, does not delay curative intent surgery) but also may lead to improved patient outcomes. Further, tumors had increased numbers of cytotoxic CD8+ T cells, the T cells primarily responsible for killing tumors. Similar studies are testing this approach with immunotherapy in a variety of other solid tumor malignancies, as access to bulk posttreatment tissue provides a unique setting to study tumor and treatment biology. Obviously, we don’t know yet if a pathologic response to immunotherapy necessarily translates to improved long-term disease-free and overall survival, but the science and rationale are sound. Only time will tell, but it’s exciting to see where the field is headed.


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Investigators Explore Neoadjuvant Immunotherapy in Hepatocellular Carcinoma
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