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The efficacy of relacorilant, a glucocorticoid antagonist, has raised concerns that routine steroid use with chemotherapy may induce resistance. This has led clinicians to reduce steroid doses, questioning a long-standing practice and its potential to blunt the therapeutic effects of chemotherapy.

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The persistent separation of survival curves in the ROSELLA trial suggests relacorilant's benefit extends beyond sensitizing tumors to chemotherapy. By acting as a glucocorticoid receptor antagonist and blocking immunosuppressive cortisol, it may also have a favorable immune-modulatory effect.

Trials adding an investigational drug to steroids for initial chronic GVHD treatment consistently fail because many patients respond to steroids alone in the short term. This early efficacy masks the new drug's potential benefit, leading to failed studies (e.g., with mycophenolate, ibrutinib, belumosudil) and a push towards new trial designs.

For rashes caused by enfortumab vedotin (EV), dupilumab is an emerging steroid-sparing treatment. It can decrease the risk and severity of EV-related rashes, offering an alternative to corticosteroids, which some clinicians worry may blunt the efficacy of concurrent immunotherapy.

The novel drug relacorilant overcomes taxane resistance in ovarian cancer by targeting glucocorticoid receptors. It blocks stress-induced steroid signaling that promotes anti-apoptotic proteins, effectively re-sensitizing tumors to chemotherapy. This represents a completely new mechanism of action for this patient population.

Though typically contraindicated, checkpoint inhibitors can be used for transplant recipients with advanced skin cancer. This requires shared decision-making, collaboration with the transplant team, and a specific protocol involving high-dose pulse steroids to mitigate the high risk of allograft rejection.

Chemotherapy is known to worsen metabolic parameters, but this should be viewed as an opportunity, not just a side effect. By actively correcting this metabolic dysfunction with adjunctive therapies, clinicians may be able to enhance the overall life-saving benefit of the chemotherapy itself.

The glucocorticoid receptor antagonist relacorilant does not require biomarker testing for patient selection. Its target is ubiquitously expressed in over 95% of ovarian cancer tissues, making it a broadly applicable therapy without the need for additional screening.

For dMMR endometrial cancer patients on combination therapy, clinicians are quicker to reduce or stop chemotherapy (like taxanes) when side effects arise. This practice reflects a growing confidence that immunotherapy is the primary driver of efficacy in this subgroup, allowing for a reduction in chemotherapy-related toxicity.

For older, transplant-ineligible myeloma patients, quadruplet regimens are not administered at full strength. Clinicians proactively reduce doses of bortezomib, lenalidomide, and dexamethasone based on patient fitness and renal function to manage toxicity while maintaining efficacy.

Clinicians must counsel patients that some drug toxicities are irreversible or create lifelong conditions. Alopecia from hedgehog inhibitors can be permanent, while immunotherapy-induced adrenal insufficiency or Type 1 diabetes require daily management, a significant quality-of-life burden for older patients.