Toxicity Profiles and Sequencing of New Oncologic Drugs

With the major themes established, Dr. Shah pushed the panel on a harder question: when a new drug shows promising results, how do you judge whether it's actually clinically meaningful and ready to change practice? Dr. Chen answered by returning to PROTEUS in detail. Patients with high-risk prostate cancer — those with high Gleason scores, extraprostatic extension, or seminal vesicle involvement — historically see recurrence in more than half of cases after prostatectomy. Adding a year of apalutamide to ADT perioperatively cut the risk of metastasis-free survival events by 20% versus placebo plus ADT. Her framework for evaluating any new result: first define the patient population, then weigh effect size against toxicity, since additional treatment "certainly, guaranteed" adds side effects even when efficacy gains aren't guaranteed. On tolerability, she noted apalutamide's signature adverse event, skin rash, affected about 30% of patients but is generally manageable, and that GU oncologists already have experience managing it from metastatic-setting use.

Dr. Luo brought the same lens to lung cancer via the adjuvant selpercatinib trial, a global phase 3 study in RET fusion–positive, stage IB to IIIA resectable non–small cell lung cancer. She emphasized that adjuvant trials carry a distinct tolerability question: can patients with no visible disease tolerate years of a drug's side effects, when that quality-of-life tradeoff looks very different than in the metastatic setting? The trial's strongly positive result moved fast — into NCCN guidelines within a week of presentation — underscoring that sequencing decisions increasingly hinge on matching a drug's toxicity profile to the specific disease setting it's being tested in, not just its topline efficacy number.