Erdafatinib was compared to chemo in the >=2nd line in patients who had FGFR2/3 mutations, fusions or alterations with metastatic bladder cancer. Survival endpoints were superior in the targeted group with a overall survival of 12 vs. eight months. In my experience, the challenge with this group of targeted agents is tolerability.
Final results from the ASPEN study confirm the strong long-term superiority of zanubrutinib over ibrutinib in symptomatic WM. While overall survival (OS) and progression-free survival (PFS) end-points are still to be reached, demonstrating the good prognosis of this disease, toxicities and response rates are much better with zanubrutinib. This is a cat-1 indication oof NCCN and a compelling option for use in this population.
Asian study of nimotuzumab (humanized EGFR-inhibitor) + gemcitabine (gem) vs. gem alone. The overall survival (OS) was 10.9 vs. 8.5 months in favor of the combination arm. While the OS difference is small, recall that the OS in the NALIRIFOX and FOLFIRINOX studies are similar. The safety profile of nimotuzumab + gemcitabine is superior to a triplet or double cytotoxic chemotherapy combination regimen. This drug is currently not available in the USA but is approved for nasopharyngeal carcinoma in China.
Phase III study of amivantamab + chemotherapy vs. chemotherapy alone as first-line therapy in patients with Exon-20 EGFR mutations. While the results of this study are impressive, one wonders what the results would be if the comparator arm were a targeted option. This is not yet reflected in the NCCN guidelines but likely will be added.
Very interesting study using tarlatamab, a bispecific T-cell engager that directs T-cells to malignant cells expressing delta-like ligand 3 (DLL3). This was a dose escalation phase II, ORR was 40% and the longevity of response in responders was impressive for this disease. Further studies are sure to come.
Osimertinib with chemotherapy improved the chance of being alive at two years compared to targeted therapy alone at 57 vs 41%. Further analysis of FLAURA2 and new studies will surely look to identify which patients benefit most from the combination of targeted therapy and chemotherapy. For young or healthy patients, this is an acceptable first line option. This is not yet reflected on NCCN but is likely to be added soon.
For metastatic urothelial carcinoma, the combination of nivolumab + gemcitabine (gem) /cisplatin (cis) resulted in an improved overall response rate (ORR) of 58 vs. 43%, progression-free survival (PFS) at 12 months of 34 vs. 22% and higher rates of complete response (CR) at 22 vs. 12%. This is the first study to improve upon the chemotherapy doublet of gem/cis in this disease setting. While an interesting treatment option, this has not yet made it into the NCCN guidelines and pembrolizumab + enfortumab seems to be a better tolerated, non-chemo option that is gaining traction.
Preliminary results of DESTINY-Lung02 show strong efficacy with trastuzumab deruxtecan (T-DXd). Overall response rate (ORR) was about 50%, with duration of response of 16.8 months. This is now FDA-approved and is an available therapy for patients with ERBB2 mutations after 1st line platinum-based chemo +/- immunotherapy. This is preferred over traditional trastuzumab or afatinib. Interestingly, some responses were seen in the ERBB2-negative patients who had over-expression by IHC. Please continue to sequence your patients and enroll in targeted therapy trials.
This is a 10-year follow-up of the ShortHER study using nine weeks vs. 12 months of adjuvant trastuzumab in HR+ non-metastatic breast cancer. With long-term follow-up, non-inferiority could not be claimed statistically. Still, the DFS/OS results are identical in those patients with N0-N3 disease, while those with N4 disease seemed to have a significant difference favoring 12 months of therapy, suggesting that volume/burden of disease drives the margin of benefit in adjuvant trastuzumab therapy.
In the EORTC-55994 study, neoadjuvant chemotherapy followed by chemoradiation + surgery was not superior to chemoradiation for patients with stage IB2 – IIB cervical cancer. However, the toxicity was acceptable, so for patients with more locally advanced disease, it could be considered. Regardless, the SOC will remain concurrent chemotherapy and radiation for these patients.
FCS Hematology Oncology Review creates a platform for our physician network to observe the most recent articles and studies available in the oncology and hematology world. By sharing these articles we are building our wealth of knowledge of new observations and treatments as they come available.
