Second-Line Toxicities After First-Line TKI in mRCC

Robert J. Motzer, MD:It’s been difficult to define whether the toxicity profile is different in the second-line for patients who have experienced toxicities in the first-line. For the most part, some of the toxicities, like hypertension, I find are less in the second-line because patients are already on antihypertensives from experience with hypertension in the first-line therapy, so they’re already into managing that.

I think that the toxicities are managed better in the second-line because there’s often experience with that toxicity for the same class of drug in the first-line. I haven’t really experienced, or been made aware of particularly, the cumulative toxicity, where toxicities seemed to be worse in the second-line because patients experience them in the first-line.

I think the most important thing is recognition of the toxicity and management. So, for all of these different compounds, it’s very important to have interaction between the doctor’s office—particularly the nurse with the patient—and communication back and forth about the specific toxicities, and have the nurses familiar with the best remedy for the adverse event.

With regard to response rate, generally patients who don’t achieve a favorable response to first-line therapy, have a briefer period of response to the second-line therapy, and it seems to happen across the board, regardless of whatever treatment program we use in second-line.

If a patient is very resistant to sunitinib in first-line, they may benefit from lenvatinib/everolimus second- or third-line, but the response is briefer than patients who achieved long-term response to sunitinib in the first-line. More aggressive tumors in first-line also translate to more aggressive tumors in second-line.

Transcript edited for clarity.

A Japanese-American Male With Recurrent RCC

November 2015

• At the age of 49, a Japanese-American man presented to the ER with abdominal pains
• CT of the abdomen and pelvis revealed diverticulitis with an incidental left renal mass (4.2 cm × 8.6 cm × 2.8 cm)
• SH: Marathon runner; nonsmoker; social drinker
• He underwent sigmoid colon resection; left radical nephrectomy
• Pathology; sigmoid colon pathology revealed diverticulitis; renal pathology revealed RCC, clear cell type
• Diagnosis: RCC stage PT2a
• KPS: 90
• Fuhrman Grade: 3/4

September 2017

• Follow-up CT showed residual soft tissue in the left nephrectomy bed, pulmonary lung metastasis, and an expansile lucent osseous lesion in the right pubic ramus
• Biopsy of one of the osseous lesions confirmed mRCC
• He began systemic therapy with sunitinib for 20 weeks and achieved stable disease and some shrinkage of the bone lesion
• KPS: 90
• MSKCC risk score: Intermediate

July 2018

• The patient now complains of left pelvic pain
• Imaging shows marked progression in retroperitoneal mass; new lung metastasis
• Laboratory values:
  • CBC: WBC - 7; Hgb - 12.6; Platelet - 190; ANC — 5.2;
  • CMP; Creatinine - 1.82 mg/dL; LFTs - WNL; Calcium - 9.2 mg/dL; LDH — WNL
• MSKCC risk score: Intermediate
• KPS: 80
• The patient was treated with palliative radiation therapy to bone metastasis
• He was then started on treatment with lenvatinib/everolimus