ASCO 2020 Update in Renal Cell Carcinoma

29 May - 31 May, 20

Virtual Meeting

29 May - 31 May, 20

Virtual Meeting

Sorafenib as Second-line Treatment in Metastatic Renal Cell Carcinoma: A Prospective Cohort

Background

Sequential inhibition of the VEGF pathway with sorafenib could be useful for patients with advanced or metastatic RCC.

Aim

To determine the activity and tolerability of sorafenib as a 2nd-line therapy in advanced RCC initially treated with a different VEGF-TKI.

Method

148 subjects with metastatic RCC, treated by nephrectomy and who had RCC progression despite treatment with sunitinib (n = 144) or pazopanib (n = 4), were included. All patients received sorafenib 400 mg orally twice a day on a continuous dosing schedule until disease progression or intolerable toxicity. The primary endpoint was time to progression

Results

The median PFS and survival after the introduction of sorafenib treatment was 8.5 months and 40.1 months respectively.
Median OS from RCC diagnosis to death was 71 months
AEs associated to sorafenib occurred in 118 (80%) subjects

Conclusions

Sequential inhibition of VEGF with sorafenib as a 2nd-line treatment may benefit patients with metastatic RCC, especially in subjects > 65 yrs old.

References

Abstract no e17077. American Society of Clinical Oncology (ASCO) 2020. Virtual Meeting. May 29-31, 2020

Pembrolizumab Plus Axitinib Versus Sunitinib As First-Line Therapy For Advanced Renal Cell Carcinoma (RCC): Updated Analysis of KEYNOTE-426

Background

The KEYNOTE-426 study demonstrated that pembrolizumab (pembro) + axitinib (axi) significantly improved OS, PFS, and ORR vs sunitinib as first-line therapy for advanced RCC (aRCC). Updated analyses are presented here.

Aim

To evaluate anti-tumor activity of pembro + axi vs sunitinib as first-line therapy for advanced RCC.

Methods

861 pts were randomly assigned 1:1 to receive pembro + axi, n = 432 or sunitinib, n = 429. Primary end points were OS and PFS. Secondary end points were ORR, DOR, and safety.

Results

Median OS was not reached with pembro + axi and was 35.7 mo with sunitinib.
For pembro +axi vs sunitinib respectively, median PFS was 15.4 vs 11.1 mo;
ORR was 60% vs 40% (P< 0.0001); CR rate was 9% vs 3%; and median DOR was 23.5 mo vs 15.9 mo.
In general, the pembro + axi benefit was observed in all subgroups tested, including IMDC risk and PD-L1 expression subgroups.

Conclusions

Pembro + axi continued to demonstrate superior and durable antitumor activity vs sunitinib in pts with first-line aRCC with a 27-mo median follow up; no new safety signals were observed.

References

Abstract no 5001. American Society of Clinical Oncology (ASCO) 2020. Virtual Meeting. May 29-31, 2020

Phase II Trial of Lenvatinib (LEN) Plus Pembrolizumab (PEMBRO) For Disease Progression After PD-1/PD-L1 Immune Checkpoint Inhibitor (ICI) In Metastatic Clear Cell Renal Cell Carcinoma (mccRCC)

Aim

To evaluate antitumor activity of lenvatinib plus pembrolizumab in pts with mccRCC with disease progression following ICI therapy.

Methods

104 pts with mccRCC, who previously had disease progression during or following ICI therapy were enrolled. Pts received LEN 20 mg orally once daily plus PEMBRO 200 mg IV every 3 weeks until disease progression or toxicity. Tumor assessments were performed every 6 weeks (until week 24), then every 9 weeks. The primary endpoint was objective response rate (ORR) at Week 24 by irRECIST.

Results

46 of 91 pts achieved a confirmed partial response for an ORR of 51%
Median PFS was 11.7 months and median DOR was 9.9 months.
The most common treatment-related adverse events (TRAEs) were fatigue (49%), diarrhea (44%), proteinuria (37%), hypertension (31%), nausea (31%), dysphonia (29%), stomatitis (29%), and arthralgia (27%). There was 1 grade 5 TRAE (upper gastrointestinal hemorrhage).

Conclusions

LEN + PEMBRO demonstrated promising antitumor activity in pts with mccRCC with disease progression following ICI therapy. No new safety signals were detected.