Experts Voice Doubts About Roche’s Polivy as First-Line Treatment for LBCL

The FDA has raised questions about the efficacy and safety of Genentech (Roche)’s Polivy (polatuzumab vedotin-piiq) when used as the first-line treatment for large B-cell lymphoma (LBCL). While this therapy has the potential to alleviate symptoms and improve the quality of life for individuals suffering from LBCL, it is important to ensure that the risks associated with its use do not outweigh the potential benefits.

The Oncologic Drugs Advisory Committee (ODAC) met on March 9 to discuss the potential approval of Polivy’s drug for a particular indication. However, the panel of experts determined that the progression-free survival (PFS) benefit was only “modest” and there was no improvement in overall survival (OS) and complete response (CR).

Polivy is an innovative antibody-drug conjugate that specifically targets B-cells by binding to their CD79b protein and delivering a powerful cytotoxic payload. In June 2019, it received accelerated approval from the FDA for diffuse large B-cell lymphoma (DLBCL) after its promising performance in the Phase Ib/II GO29365 study. This groundbreaking treatment revolutionizes the fight against blood cancer and offers new hope to patients.

Genentech launched the Phase III POLARIX trial to ensure Polivy remained a viable treatment option for DLBCL patients. According to Levi Garraway, M.D., Ph.D., chief medical officer and head, Global Product Development, Genentech, the trial was designed to position Polivy as the “new standard of care” for the first-line treatment of DLBCL.

Researchers recently conducted a trial to test the efficacy of an innovative combination drug regimen, dubbed “pola+R-CHP,” which combines the drug Polivy with Rituxan (rituximab), cyclophosphamide, doxorubicin, and prednisone. The efficacy of pola+R-CHP was evaluated by measuring Progression-free Survival (PFS) and was compared to that of the current standard of care in Diffuse Large B-Cell Lymphoma (DLBCL), known as R-CHOP.

Polarix, a groundbreaking study, has demonstrated that Pola+R-CHP boosts Progression-Free Survival (PFS) by a remarkable 27%. This exciting outcome has prompted Genentech to submit a supplemental Biologics License Application to the FDA, with the hope of bringing Polivy to the forefront of cancer treatment.

Genentech has presented compelling proof that pola+R-CHP is both safe and effective, showing a clinically meaningful benefit with a safety profile similar to that of R-CHOP. Thursday’s meeting will present further evidence of POLARIX’s effectiveness and safety.

The FDA’s Concerns

The FDA advisors acknowledged Polivy’s PFS benefit was statistically significant, yet the magnitude of its effect was deemed to be relatively small. Raising the question of whether the rate of difference was truly clinically meaningful.

The latest review by the U.S. Food and Drug Administration (FDA) has revealed that the Polivy regimen of pola+R-CHP has had little to no effect on improving overall survival (OS) or cancer remission (CR). After a median follow-up time of 39.7 months, the pola+R-CHP regimen only reduced the risk of death by 6% compared to the R-CHOP regimen, an effect that failed to reach statistical significance.

At POLARIX’s earliest stages, and in patients with DLBCL, the R-CHOP arm showed a distinct advantage in terms of overall survival. This finding was particularly encouraging, suggesting that the R-CHOP protocol had a beneficial impact in these patients.

The safety and efficacy of frontline therapy for LBCL has not seen an improvement in overall survival, despite the low event rates and associated uncertainties. This lack of improvement further adds to the benefit-risk uncertainties.

Results from the study showed that Polivy had a modest benefit in terms of disease-free survival, duration of response and event-free survival but did not significantly increase the overall cure rate.

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