durvalumab after chemoradiation for NSCLC

[seper]

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For stage IIIB lung cancer, if the chemotherapy regimen is paclitaxel plus carboplatin, do MedOncs complete 2 cycles of consolidative paclitaxel plus carboplatin q21 days and then start durvalumab? Or forgo consolidatiive pac/carbo altogether? Any data to support either approach? Thanks.

 

[evilbooyaa]

Some med oncs prefer to give cis/etop or carbo/etop or carbo/alimta so they don't have to deal with consolidation. The ones who stuck with CarboTaxol skip the consolidation in favor of Durva.

Med-oncs shouldn't be consolidating without Durva anymore IMO. Maybe some are doing CarboTaxol + Durva, idk. Subgroup analysis on Pacific (scatter plot in supplementary) showed greater benefit of Durva when given within 14 days of completion of RT - I would not want that time frame elongated.

 

[scarbrtj]

This is kinda scary even though N=1.

Apparent Immunotherapy-Induced Hyperprogression in a Patient With Stage III NSCLC

 

[medgator]

I've just seen Carbo taxol concurrent with xrt, skip consolidation and proceed on to durva ~1 month later.

Didn't know a shorter interval might be better

 

[evilbooyaa]

Didn't know a shorter interval might be better

Figure S1 of the 2018 update in NEJM: https://www.nejm.org/doi/full/10.1056/NEJMoa1809697

Outcome for this table is OS, not PFS.

*EDIT* - As an aside - I'm actually somewhat concerned about the HR crossing 1 in patients treated after the 14 day cut-off (as the protocol was amended from mandating initiation within 14 days to then allowing treatment after 14 days).... 350/175 patients in experimental/placebo arm that didn't show a significant benefit on subgroup analysis at > 14 day initiation.... but 120/62 showed a huge benefit at < 14 day initiation. Wouldn't change how I treat based on initiation time, but I will try to push for earlier initiation when possible (lack of significant toxicity). Something something about RT setting up the APCs and T-cells the most at a short time frame after definitive RT allowing the IT-super charged immune system to knock them down.

However, could just be lack of statistical power for something that is of smaller benefit than early initiation.

I think if concurrent IT is tolerable with RT (forget if the next PACIFIC is evaluating Durva + Chemo or Durva alone as the experimental arm) that'll be the future.

 

[Haybrant]

z

This is kinda scary even though N=1.

Apparent Immunotherapy-Induced Hyperprogression in a Patient With Stage III NSCLC

Hyperprogression is a thing that can be induced by immunotherapy? Is it actual progression of disease? I assume you stop the immunotherapy, then what do you do? The case I’m referring to the guy had very significant mediastinal progression after excellent initial response to chemo/RT

 

[evilbooyaa]

Yes, caused by the immumnotherapy. There was an educational talk about it at the Multidisciplinary Thoracic Cancers Symposium given by Christophe Le Tourneau. It's rare but exists.

Hyperprogression as a distinct outcome after immunotherapy - PubMed

Cancer research is living a time of unparalleled expectations around immunotherapy, a therapeutic strategy that materializes the elegant idea of weaponizing our immune system to eradicate tumor cells. In an everchanging standard of care, a growing number of studies have shown that immunotherapy...

www.ncbi.nlm.nih.gov

Hyperprogressive Disease Is a New Pattern of Progression in Cancer Patients Treated by Anti-PD-1/PD-L1 - PubMed

<span><b>Purpose:</b> While immune checkpoint inhibitors are disrupting the management of patients with cancer, anecdotal occurrences of rapid progression (i.e., hyperprogressive disease or HPD) under these agents have been described, suggesting potentially deleterious effects of these drugs...

www.ncbi.nlm.nih.gov

And AFAIK, it is actual progression of disease. The IT essentially plays for the wrong team, and the patient casesdescribed in the educational talk either went straight to hospice or briefly attempted non IT systemic therapy.

 

[Palex80]

This is kinda scary even though N=1.

Apparent Immunotherapy-Induced Hyperprogression in a Patient With Stage III NSCLC

I've seen it in stage IV disease too. Although it is very uncommon as far as my med oncs tell me.
On the other hand, I've also seen a few testicular cancer / hodgkins lymphoma patients dying within weeks after receving bleomycin.
Drugs are drugs and they come with toxicity.

 

[Palex80]

For stage IIIB lung cancer, if the chemotherapy regimen is paclitaxel plus carboplatin, do MedOncs complete 2 cycles of consolidative paclitaxel plus carboplatin q21 days and then start durvalumab? Or forgo consolidatiive pac/carbo altogether? Any data to support either approach? Thanks.

We know that chemotherapy before chemo-RT (Vokes) does not lead to an OS benefit and we also know that consolidation chemotherapy after chemo-RT (Hanna) does not lead to an OS benefit either. So, "more" chemo "around" chemo-RT is not beneficial.

If you take a look at the PACIFIC publication (2017 paper) you will find the chemotherapy regimes used in the supplementary material pdf.
99.7% of all patients had concurrent chemo-RT and it looks as if 26.8% also had additional induction chemo before chemo-RT.
No patients had consolidation chemotherapy.