Clinical trials show a sustained overall survival benefit for upfront chemo-immunotherapy in dMMR patients, even with over 90% of the placebo group receiving immunotherapy upon progression. This demonstrates that delaying immunotherapy fails to rescue outcomes, making upfront use critical.
While PARP inhibitors plus immunotherapy (e.g., in the RUBY-2 trial) improved progression-free survival (PFS) in pMMR endometrial cancer, the overall survival (OS) curves crossed, showing no OS benefit. This cautionary signal suggests the combination may not be advantageous long-term and requires further investigation.
A patient recurring five years after initial chemotherapy is considered platinum-sensitive and likely to respond to chemotherapy again. This long interval means that re-treatment with a chemo-immunotherapy combination is a strong option, even if newer targeted agents are also available, as the tumor has not demonstrated recent chemo-resistance.
Even in Stage 1 uterine serous cancer, HER2 positivity is associated with a 50% recurrence rate, compared to 17% for HER2-negative patients. This highlights HER2 as a powerful negative prognostic marker independent of stage and underscores the need for aggressive treatment or targeted therapies like trastuzumab.
Clinicians recommend starting lenvatinib at the full 20mg dose rather than escalating from a lower dose. This ensures therapeutic levels are reached. They then dose-reduce aggressively as needed. Starting low risks falsely concluding the drug is ineffective if the patient tolerates a suboptimal dose without response.
The SIENDO trial showed that the nuclear transport inhibitor selinexor may improve outcomes as a maintenance therapy specifically for p53 wild-type endometrial cancer. This is a novel approach that uses a 'normal' biomarker, rather than an aberration, to identify patients who are likely to benefit from treatment.
When a patient on lenvatinib and pembrolizumab develops diarrhea, the first diagnostic step is to pause lenvatinib. If the diarrhea resolves, it's likely from the TKI. If it persists, it's more likely immune-mediated colitis from pembrolizumab, requiring different management like steroids. This simple step clarifies the cause.
The PORTEC3 study revealed that the benefit of adding chemotherapy to pelvic radiation was concentrated in patients with p53-abnormal tumors. In contrast, those with POLE-mutated or mismatch repair deficient (dMMR) cancers saw little to no benefit, suggesting molecular subtypes should guide adjuvant therapy decisions.
Despite NCCN guidelines placing POLE testing first in the hierarchy, many US institutions do not perform it routinely because it currently does not alter standard-of-care treatment. Clinicians often only order the send-out test when a specific clinical trial (like RAINBO) requires it to de-escalate care.
As more antibody-drug conjugates (ADCs) become available, a key concern is resistance to the cytotoxic payload. If a tumor develops resistance to a topoisomerase-1 inhibitor from one ADC, it may not respond to other ADCs using the same payload, regardless of their different antibody targets, complicating future treatment sequencing.
Interstitial lung disease (ILD) is a serious risk with trastuzumab deruxtecan (TDXD). Oncologists must take it extremely seriously, engaging a pulmonologist immediately at the first sign of symptoms or CT scan findings. A collaborative, multidisciplinary approach is essential for safely managing this potentially fatal toxicity.