Stage IIIb ALK NSCLC first line treatment

This question is not for a specific patient, it is designed to understand how oncologists would approach this problem. There’s a 50 year old stage IIIb unresectable NSCLC patient with ALK positive FISH biopsy result. PD-L1 25%. ECOG 0-1. Should this patient be treated first line with Chemoradiation+Durvalumab or Alectinib? Would the recommendation be any different with EGFR mutation?

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Jim C GRACE Co…
Posts: 147

GRACE Community Outreach Team

Hello, Welcome to GRACE. Stage IIIb NSCLC, if unresectable, is typically treated with a combination of chemotherapy and radiation in an effort to cure the cancer, but as in any case there may be individual factors (such as the overall health of the patient or location of the tumor) which may suggest a different course of action. Systemic treatments alone, such as chemotherapy, targeted therapy or immunotherapy, are not expected to result in cure, although there are exceptions. The choice of chemoradiation would generally be the same regardless of which activating mutation/rearrangement, such as ALK or EGFR, is present. Jim C Forum Moderator

JanineT GRACE …
Posts: 657
GRACE Community Outreach Team

Jim I can't imagine I'd disagree so it's very possible I'm reading something wrong, but...

 

The PACIFIC trial shows that there is a significant improvement in overall survival when Durvalumab is added after chemo radiation in stage III unresectable nsclc in those with at least 1% pd 1 expression with only  minimal added toxicities.  I think most oncs are using this plan and even calling it a game changer.  

 

Here are a couple of videos from onclive,

https://www.youtube.com/watch?v=NsGbakdhsGU

https://www.onclive.com/peer-exchange/nsclc-io-combinations/the-pacific-trial-in-stage-3-nsclc

From September 2018 New England Journal of Medicine, "Durvalumab therapy resulted in significantly longer overall survival than placebo. No new safety signals were identified. (Funded by AstraZeneca; PACIFIC ClinicalTrials.gov number, NCT02125461.)"

 

https://www.nejm.org/doi/full/10.1056/NEJMoa1809697

Edited to add, as a lay person I often go directly to the discussion and or conclusion of trial abstracts.  They get complecated quickly.  

 

All best,

Janine

 

 

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

JanineT GRACE …
Posts: 657
GRACE Community Outreach Team

Here it is official, "On February 16, 2018, the Food and Drug Administration approved durvalumab (Imfinzi, AstraZeneca Inc.) for patients with unresectable stage III non-small cell lung cancer (NSCLC) whose disease has not progressed following concurrent platinum-based chemotherapy and radiation therapy."  https://www.fda.gov/drugs/informationondrugs/approveddrugs/ucm597248.htm  and I believe the most recent overall survival data is newer than the Feb approval which adds more proof of its efficacy.

I joined GRACE as a caregiver for my husband who had a Pancoast tumor, NSCLC stage III in 2009. He had curative chemo/rads then it was believed he had a recurrence in the spine/oligometastasis that was radiated. He's 10 years out from treatment.

Jim C GRACE Co…
Posts: 147

GRACE Community Outreach Team

Janine,

Thanks for clarifying my answer. as I addressed only the question of whether chemoradiation was appropriate as initial therapy, and whether the choice would be the same whether there was an EGFR or ALK mutation/rearrangement. As you state, after chemoradiation then durvalumab is indicated.

Jim C Forum Moderator