Medical Oncology
Physician insights on cancer treatment protocols, immunotherapy, targeted therapies, and clinical trial updates.
Recent Discussions
In light of the 2024 Shkreli Awards, how do you address patient concerns regarding the 240 mg versus 960 mg dose of sotorasib?
The randomized dose comparison study of sotorasib 960 mg versus 240 mg was conducted as part of an initiative from the US FDA Project Optimus, based on observations in the early phase dose-escalation study demonstrating non-dose proportional increases in drug exposure at dose levels of about 180 mg ...
What clinical and pathologic features do you use to discern whether >= 2 synchronous lung nodules, biopsy proven lung adenocarcinoma, are different primaries versus metastatic disease?
These cases are always discussed at a multi-disciplinary tumor board with a review of pathology slides from the operative specimen. In some cases, there are clearly different morphologies or levels of differentiation. These can be initial clues, but not definitive to determine synchronous primaries ...
Is there any evidence that patients with metastatic NSCLC with KRAS G12C mutations benefit less from treatment with immunotherapy?
KRAS mutation in NSCLC has been associated with improved response rate and overall survival compared to KRAS wild type NSCLC in meta-analysis of single-agent, second-line trials with PD-1/PD-L1 inhibition. Moreover, analysis of patients with KRAS lung adenocarcinoma divided by subsets including co-m...
What is your current practice for obtaining PD-L1 and mutation testing for newly diagnosed metastatic NSCLC?
PD-L1 testing is done reflexively in my institution. Molecular testing needs to be ordered by oncology. When I see patient in the initial consultation, I already have PD-L1 expression available. I strongly believe in next generation sequencing for my lung cancer patients as it preserves tissue. Curr...
Which targeted therapies should we be more cautious of giving after recent immunotherapy in NSCLC?
In general, one should be cautious. Phenomenon of increased toxicity with immune checkpoint inhibitors (ICIs) plus targeted therapies such as EGFR TKI (pneumonitis, hepatotoxicity or dermatologic toxicity), ALK TKIs (mostly hepatotoxicity) or BRAF inhibitors (hepatotoxicity, dermatologic) were obser...
What are your top takeaways in Thoracic Cancers from ASCO 2023?
Always so hard to pick a top 3 as luckily each ASCO provides us with a broad spectrum of significant advances in our field but if pressed against the wall, I might pick below 3: The first is a double dip choice I admit matching ADAURA with KN789. Of course, you need to be living in a cave not to be ...
Is there any evidence that sotorasib is effective in KRAS-driven tumors beyond KRAS G12C?
The short answer is no, sotorasib does not have efficacy in KRAS mutant tumors beyond KRAS G12C. KRAS activates downstream signaling by actively cycling from GTP to GDP, and exists in both GTP and GDP states. The cysteine residue at the covalent binding pocket under switch II in the inactive GDP sta...
Are there best practices for managing or mitigating toxicity from sotorasib such as hyperbilirubinemia or edema?
Personally, I think it is important to monitor closely so that any adverse events could be detected early and acted upon quickly. Based on the package insert of sotorasib (lumakras_pi_hcp_english.pdf), liver function tests should be monitored every 3 weeks for the first 3 months of treatment then on...
How do you approach treatment sequencing in KRAS G12C NSCLC?
Sequencing is an excellent question that will require a little more time to be answered. There are currently multiple ongoing trials in this space but at the current moment, the approval of sotorasib is in the second line space and I would not use KRAS inhibitors as first line off study. That being ...
What are your treatment considerations for a patient with stage IVb NSCLC who is KRAS G12C mutated and PD-L1 high (>50%)?
Assuming that this is in the treatment naïve scenario, we have a lot of options in this case. The patient could be considered single agent immunotherapy or chemo-immunotherapy or clinical trials for KRAS G12C. While we need more prospective data on this topic, I still look at the co-mutations (i.e.,...