How do you proceed with treatment of a patient with stage IIIB NSCLC who progresses DURING treatment with concurrent weekly carboplatin/paclitaxel and radiation?

Assuming no clinical trial, no actionable mutation, and PD-L1 < 50%, do you consider the patient to be primary refractory to platinum and move to single agent immunotherapy or would you consider chemoimmunotherapy vs nivo/ipi?

2 Answers

Mednet MemberInvited Expert

Medical Oncology · Wexner Medical Center at The Ohio State University

Answered on

I have been looking at this question for a little over a week, and struggling to know how to answer this. The relevant trials for a patient with PDL1 somewhere between 0 and 49% (KEYNOTE-189, KEYNOTE-407, KEYNOTE-042, CheckMate 227, and 9LA) would have excluded patients who received either adjuvant chemotherapy or definitive chemoradiation within the last 6 (or 12) months, hence coming up with a treatment for someone who has progressed during chemo-RT is based upon intuition and extrapolation as much as it is based upon data. The first comment to explicitly state here is that knowing the genetics of the tumor is now incredibly important. Many (but not all) institutions will get molecular testing on patients with stage 3B cancers not because it will impact treatment now, but in the event of recurrence/relapse/progression when targeted therapy for an appropriate target would be the optimal choice. If it hasn't been done previously, now it is critical to get this information.

With that noted, there are some general caveats to the answer I will give, I assume 1) the patient continues to retain appropriate functional status, 2) that the molecular characteristics are without actionable targets, 3) this progression is not "oligo" progression that might be appropriately treated with SRS or SBRT (for example within the CNS), and 4) that there is no appropriate clinical trial for this patient.

There are a couple of options for first line metastatic treatment that could be considered: Pembrolizumab alone (assuming PDL1 is between 1 and 49%), Chemo + Pembrolizumab, Nivolumab + Ipilumumab, and Chemo (for two cycles) + Nivolumab + Ipilumumab. Again, in the absence of true data, I would probably not be enthusiastic about Pembrolizumab alone (and even if PDL1 were > 50%, I'm not sure I would want to do this). I have, in the past, treated similar patients with Chemo + Pembrolizumab and been somewhat disappointed. Hence, with the time honored tradition of treating your next patient based upon experiences (good or bad) you have had most recently, just last week, I had two similar patients (who either progressed while receiving chemro-RT or shortly thereafter (with new malignant pleural effusions), I have elected to proceed with Nivolumab and Ipilumumab.

You might want to ask me how I feel about this strategy in ~ 2 months.

Mednet Member

Medical Oncology · Siri Onclogy and hematology Infusion Service

Answered on

This is a low platinum dose. I would most likely switch to chemo and immunotherapy. I would be concerned about pneumonitis with a combined immunotherapy approach initially with the near use of radiation. If after 2 cycles the response is unsatisfactory, one could try then an ipi, nivo approach.