Amol Akhade: Promising Results in Recurrent Low-Grade Serous Ovarian Cancer
Amol Akhade, Consultant Medical Oncologist at Suyog Cancer Clinics, shared a post on LinkedIn:
“Promising Results in Recurrent Low-Grade Serous Ovarian Cancer (LGSOC)
The ENGOT-OV60/GOG-3052/RAMP 201 Phase 2 trial evaluating Avutometinib (MEK1/2 inhibitor) ± Defactinib (FAK inhibitor) has delivered encouraging outcomes in patients with recurrent LGSOC — a rare, difficult-to-treat, and often chemoresistant disease.
Mechanism of Action:
Avutometinib targets the MAPK pathway (MEK1/2), while Defactinib inhibits FAK, a key regulator of the tumor microenvironment and a contributor to adaptive resistance. The combination aims to block both tumor-intrinsic signaling and stroma-driven survival cues, improving depth and durability of response.
Why KRAS Matters:
KRAS mutations (seen in ~30–50% of LGSOC) lead to constitutive activation of MAPK signaling, making MEK inhibition a logical target. The trial demonstrates that KRAS-mutant tumors are more “MAPK-addicted”, hence more responsive to this combination.
Key Results (Combination Arm):
ORR: 31% overall
- 44% in KRAS-mutant
- 17% in KRAS wild-type Median PFS:
- 22.0 months (KRAS-mutant)
- 12.8 months (KRAS wild-type) Median DOR: 31.1 months Responses seen even in MEKi-pretreated patients
Safety:
Most adverse events (e.g., nausea, rash, blurred vision, fatigue) were low grade and manageable with dose modifications. Treatment discontinuation due to toxicity was rare.
What’s Next?
A Phase 3 confirmatory trial (RAMP 301 / GOG-3079 / ENGOT-ov83) is already underway (NCT06072781), using PFS as the primary endpoint.
Takeaway:
The Avutometinib + Defactinib combination shows real potential to become a new standard in recurrent LGSOC — particularly for patients with KRAS mutations, who have limited options.”
Title: Efficacy and Safety of Avutometinib ± Defactinib in Recurrent Low-Grade Serous Ovarian Cancer: Primary Analysis of ENGOT-OV60/GOG-3052/RAMP 201
Authors: Susana N. Banerjee, Els Van Nieuwenhuysen, Carol Aghajanian, Véronique D’Hondt, Bradley J. Monk, Andrew Clamp, Emily Prendergast, Ana Oaknin, Kari Ring, Nicoletta Colombo, Robert W. Holloway, Manuel Rodrigues, Hye Sook Chon, Charlie Gourley, Alessandro D. Santin, Premal H. Thaker, Christine Gennigens, Gregg Newman, Erin Salinas, Hagop Youssoufian, Kathleen N. Moore, Stephanie Lustgarten, David M. O’Malley, Toon Van Gorp, Rachel N. Grisham
Read the Full Article on Journal of Clinical Oncology
More posts featuring Amol Akhade.
-
Challenging the Status Quo in Colorectal Cancer 2024
December 6-8, 2024
-
ESMO 2024 Congress
September 13-17, 2024
-
ASCO Annual Meeting
May 30 - June 4, 2024
-
Yvonne Award 2024
May 31, 2024
-
OncoThon 2024, Online
Feb. 15, 2024
-
Global Summit on War & Cancer 2023, Online
Dec. 14-16, 2023