**10. Role of immunotherapy**

ATC shows high expression of PD-1/PDL-1, and hence immunotherapy may be a promising approach in these patients. However, data available on its use in ATC are limited. Many phase II trials are ongoing with immunotherapy alone as well as in combination with other agents.

The combination of Pembrolizumab and Lenvatinib in ATC is evaluated in the phase II trial of ATLEP (Anaplastic Thyroid Carcinoma Lenvatinib Pembrolizumab) study and has shown a partial response of 37.5% [53]. Also, a single institution study by Lorch et al. has reported partial response in one-third of the ATC patients treated with a combination of Ipilimumab and Nivolumab [54].

Another PD-1 inhibitor Spartalizumab was tested by Capdevila et al. in 41 heavily pretreated ATC patients and showed a response rate of 19.6%. The median OS was 5.9 months with 40% alive at 1 year. The median PFS was 1.7 months. The response rate was higher for those who had a greater PDL-1 expression (35%) [55]. But, the drug is not FDA approved and is not commercially available.

#### *Thyroid Cancer – The Road from Genes to Successful Treatment*


#### **Table 4.**

*Newer drugs and their clinical trials.*

#### **Figure 1.**

*Stage IVA treatment approach.*

Many newer drugs are being tested in phase II and III trials for ATC due to its aggressive nature and poorer outcomes than conventional treatment. A few are listed in **Table 4**.

Stage-wise treatment approach is summarized in **Figures 1**–**3**. Clinical trials are encouraged and the best supportive care can be considered as an option at any point of treatment.
