For a patient with metastatic NSCLC, PD-L1>50%, after progression on first line checkpoint inhibitor, do you prefer chemotherapy alone or chemotherapy added to the immunotherapy?

In general, I would say that chemotherapy alone would be the recommendation with the caveat that if disease progression can be treated ablative, then I continue pembrolizumab (I've had only 1 or 2 patients who fall into this category).

I base this impact on a number of case reports as well as a smal...

I think that the only supportable plan would be the use of chemotherapy alone or perhaps a clinical trial if one could be designed and completed for this circumstance. The seat of my pants has become rather threadbare over the course of my career when I tried to impose a conclusion on the basis of c...

I agree with the answers provided by @Dr. First Last and @Dr. First Last and only want to add that this question will potentially be answered in the INSIGNA trial (ECOG-ACRIN-EA5163: A Randomized, Phase III Study of Firstline Immunotherapy Alone or in Combination with Chemotherapy in Induction/Maint...

Clinical trials are preferred, if available, and chemo if there is frank, non-oligometastatic progression. If there's a mixed response, you may add chemo to pembrolizumab. If there is oligometastatic progression, I would refer for ablative radiation then resume pembrolizumab afterward.

There are no prospective trials to guide us in this situation. I assume that we are discussing patients that had an initial benefit to immunotherapy such as response or prolonged stability and are now progressing. In those patients, I generally prefer to stop immunotherapy unless we are faced with o...

I think at present, the question as to the continued benefit of immunotherapy beyond progression is certainly a research question - for example, addressed in the pivotal INSIGNA study and would not make a general recommendation for its use. However, there are definitely some datasets that make this ...

I'd recommend chemotherapy alone, but there is a dearth of published data.

One of the reasons why patients with high expression of PD-L1 who progress after frontline checkpoint inhibitor therapy are offered chemotherapy in the first place is the slow progress in developing sequential I-O agents against novel targets such as LAG-3, TIGIT, and TIM-3 (Horvath et al., PMID 329...

We still don't know that anything is better than chemotherapy (+/- ramicirumab) alone - and unfortunately, that leaves us with docetaxel. We have to find a way forward from that.