Indian Natco Cabozantinib

Product Name: Cabozantinib

English Name: Cabozantinib

Specifications: 20 mg × 30 capsules/box; 40 mg × 30 capsules/box; 60 mg × 30 capsules/box

Manufacturer: Natco Pharma

Cabozantinib is a multi-targeted, broad-spectrum anticancer drug capable of inhibiting at least nine distinct targets, including MET, VEGFR1/2/3, ROS1, RET, AXL, NTRK, and KIT.

Currently, Cabozantinib has demonstrated significant therapeutic efficacy across a wide range of solid tumors—including kidney, thyroid, liver, soft tissue sarcoma, non-small cell lung, prostate, breast, ovarian, and colorectal cancers—with particularly outstanding results in controlling bone metastases. Due to its broad effectiveness against multiple cancer types, Cabozantinib is often referred to as the "universal remedy" among targeted therapies, possessing broad-spectrum anticancer capabilities.

Treatment of Renal Cell Carcinoma: Cabozantinib demonstrates an objective response rate several times higher than that of Sutent (46% vs. 18%), accompanied by a significant prolongation of overall survival (30.3 months vs. 21.8 months). The side-effect profiles of both drugs are quite similar, with adverse event rates standing at 67% and 68%, respectively. The primary side effects include diarrhea, fatigue, hypertension, and hand-foot syndrome. Currently, Cabozantinib has become a preferred first-line treatment option for advanced kidney cancer.

Treatment of Hepatocellular Carcinoma: In patients with advanced liver cancer treated with Cabozantinib, overall survival was significantly prolonged, and the risk of mortality was reduced by 37%. The objective response rate is approximately 5%. Currently, alongside drugs such as Regorafenib and PD-1 antibodies, Cabozantinib has established itself as a key therapeutic agent for the treatment of advanced liver cancer.

Treatment of Lung Cancer: Among patients with non-small cell lung cancer (NSCLC), approximately 2% harbor *RET* gene rearrangements. These patients are eligible for treatment with Cabozantinib. In 2016, the prestigious medical journal *The Lancet Oncology* published clinical trial data regarding the use of Cabozantinib in lung cancer patients with *RET* rearrangements: among 26 patients, the objective response rate was 28%, and the disease control rate approached 100%. Furthermore, for lung cancer patients with wild-type EGFR whose first-line treatment has failed, the use of Cabozantinib in combination with Tarceva (Erlotinib) significantly extends survival compared to using either Cabozantinib or Tarceva alone. The median survival in the combination therapy group was 13.3 months, compared to 9.2 months in the Cabozantinib monotherapy group and 5.1 months in the Tarceva monotherapy group.

Treatment of Thyroid Cancer: For thyroid cancer patients harboring *RET* mutations, Cabozantinib significantly prolonged overall survival, extending it from 18.9 months to 44.3 months—more than a twofold increase. In the overall patient population, overall survival was also extended from 21.1 months to 26.6 months.

Cabozantinib targets numerous molecular pathways; some of these targets are involved in the formation of bone metastases. Consequently, the drug demonstrates excellent efficacy in controlling bone metastases associated with solid tumors and has been widely utilized in the treatment of bone metastases arising from renal cell carcinoma and prostate cancer.

Cabozantinib can enhance the efficacy of immunotherapies—such as PD-1 antibodies—by mechanisms that include eliminating "myeloid-derived suppressor cells" (MDSCs) located within the tumor microenvironment, which otherwise act to suppress the immune response. As a result, numerous studies have identified Cabozantinib as an "ideal partner" for PD-1 antibodies, utilizing the combination in therapeutic regimens that have yielded favorable clinical outcomes.

Indications:

Cabozantinib has a broad range of indications, primarily including:

(1) Advanced renal cell carcinoma in patients who have previously received anti-angiogenic therapy;

(2) Medullary thyroid carcinoma that is unresectable (cannot be surgically removed);

(3) Hepatocellular carcinoma (liver cancer) in patients who have developed resistance to Nexavar (Sorafenib);

(4) Advanced prostate cancer in patients with bone metastases.

Dosage and Administration:

(1) The recommended dosage is 140 mg daily (consisting of one 80 mg capsule and three 20 mg capsules);

(2) The medication must not be taken with food;

(3) Patients should refrain from eating for at least 2 hours—specifically, for at least 1 hour before taking the medication and for at least 1 hour after taking it;

(4) In the event of adverse reactions, dose reduction or temporary interruption of treatment may be considered. Adverse Reactions:

The most commonly reported adverse drug reactions (≥25%) associated with cabozantinib are diarrhea, stomatitis, palmar-plantar erythrodysesthesia syndrome (PPES), weight loss, decreased appetite, nausea, fatigue, oral pain, hair color changes, dysgeusia, hypertension, abdominal pain, and constipation.