Instead of presenting the entire treatment plan upfront, clinicians introduce the Amphorte regimen (lurbinectedin maintenance) after 2-3 cycles of induction chemo-IO, once a patient has shown a response. This avoids overwhelming patients on day one and allows for a more focused discussion when the decision is relevant.
The IMFORTE trial saw a 25% attrition rate between induction and randomization for maintenance therapy. This reflects the clinical reality that a significant portion of patients are too debilitated by initial chemo-IO to be candidates for intensified maintenance, making immunotherapy alone a reasonable alternative for them.
Since the IMFORTE trial excluded patients with brain metastases, oncologists hold differing views. Some are purists and avoid it off-protocol, while others explain the lack of evidence (which isn't negative evidence) to the patient and consider it, especially if CNS disease is controlled, creating a personalized decision-making scenario.
While initial doses of the BiTE therapy tarlatumab require inpatient monitoring for CRS and ICANS, experienced centers are shifting to outpatient administration for subsequent cycles. This is typically for low-risk patients with good support who live nearby, signaling a move towards more manageable community use.
A critical logistical challenge for administering Tarlatumab is ensuring patients with fever (a potential sign of CRS) are not left waiting in a standard emergency room. An effective strategy involves creating a dedicated protocol so these patients are seen immediately by staff familiar with the drug's toxicities, preventing dangerous delays.
The challenging side effect of taste loss (dysgeusia) from tarlatumab is not always permanent. Clinicians observe that while the nadir occurs around 8-12 months, taste can significantly improve for patients who remain on therapy for extended periods (e.g., up to two years), encouraging perseverance through this difficult toxicity.
The SESA phase 2 trial is exploring a potentially paradigm-shifting approach by randomizing first-line SCLC patients to either standard chemo-immunotherapy or a novel combination of the SEZ6-targeting ADC (ABV-706) plus immunotherapy. This could represent the first fully platinum-free option for these patients.
With 18 of 19 ADCs in development for SCLC using a topoisomerase-1 inhibitor payload, there's a significant risk that patients may not respond to a second ADC after progressing on a first. This highlights a critical need to develop ADCs with alternative payloads to provide more therapeutic options and overcome resistance.
When patients with EGFR-mutant adenocarcinoma transform to small cell lung cancer and then progress on SCLC-directed therapy, it's essential to perform another biopsy. The histology can switch back to the original adenocarcinoma, which would completely alter the next line of treatment, highlighting the tumor's dynamic heterogeneity.
For the rare case of resected, node-positive (N2) early-stage SCLC, some clinicians give four courses of adjuvant chemo-immunotherapy, followed by maintenance IO. While not based on a dedicated trial in this specific surgical setting, it's an extrapolation from the positive ADRIATIC study in non-surgical limited-stage disease.
With Tarlatumab becoming a standard in the relapsed setting, the question of what comes next is critical. Experts envision sequencing ADCs like ifanatamab deruxtecan or sacituzumab govitecan immediately after progression on the T-cell engager, highlighting the need for effective therapies in the post-BiTE landscape.