Episode 034: Lung Cancer Series, Pt. 11: NSCLC Capstone with Dr. Jack West

Lung cancer is one of the most commonly diagnosed type of cancer and so it is fitting that we start the first of our disease-specific oncology series with this diagnosis. This week, we begin to round out our NSCLC series with the first of two episodes where we interview Dr. Jack West from City of Hope!

We strongly recommend you listen to our previous episodes on early stage lung cancer (Episodes 026 and 029) to follow along in this discussion. Key trials mentioned in this episode include:

ADAURA Trial

IMPOWER010

CHECKMATE816

Q: We’ve previously discussed that adjuvant cisplatin doublet chemotherapy is used for tumors > 4cm and/or nodal involvement. Given that PD-L1 status and EGFR status can also potentially change adjuvant therapy choices, how do you employ these tests in your practice?

* Different approaches at every center/with different thoracic oncologists.

* Dr. West does NOT recommend sending broad NGS testing on everyone if it is not going to change management.

* It it may influence management, at the very least, PDL1 and EGFR should be performed because of implications on adjuvant treatment options (See Episode 026 for treatment discussions):

** ADAURA Trial: Adjuvant Osimertinib x3 years for EGFR+ patients

** IMPOWER010: In patients with PDL1 >50%, patients did better with 1 year of immunotherapy (atezolizumab) after adjuvant therapy

* In patients with higher risk disease, can consider sending broad NGS, particularly looking for ALK and other mutations; remember that EGFR and ALK+ patients do NOT respond to immunotherapy well. This is important because we don’t want to give someone side effects that they would not otherwise had (these patients are getting treatment adjuvantly AKA after their disease is already resected!)

Q: What are limitations of the ADUARA Trial?

* The ADUARA suggested disease-free survival advantage with use of osimertinib, but we don’t know final overall survival data yet.

*Limitations:

** Three years of therapy

** Very expensive drug

** More data presented at ESMO 2022 on efficacy; Dr. West stated that there appears to be drop off in survival after stopping drug. Overall survival data not yet available

* Just because patients can get osimertinib does NOT mean that they are not eligible for chemotherapy

**Adjuvant chemotherapy for patients provides long-term benefit

** JBR.10 Trial: Older trial, but showed that patients who got adjuvant treatment (in this case vinorelbine plus cisplatin) had prolonged disease-free and overall survival in early-stage non–small-cell lung cancer.

** Follow up study suggested that EGFR+ patients trended towards longer survival

Q: What are your thoughts on Checkmate 816 with the use of neoadjuvant nivolumab in addition to the platinum doublet? Do you think pathologic CR was an appropriate surrogate endpoint for the trial?

* Complete path CR is a new end-point, but it does correlate with PFS. We cannot always for traditional endpoints, such as overall survival data, to mature because doing so may result in us withholding therapy that may be very beneficial.

* Biggest benefit to neoadjuvant treatment is that more patients are able to get the full regimen. Many have complications after surgery and never are able to then get/benefit from chemotherapy. Supported by data from NATCH trial

Q: What are your thoughts on induction chemoradiation vs. chemotherapy alone?

* Dr. West prefers to not use radiation pre-operatively, with some exception (for instance, pancoast tumor)

Tune in next week for part 2 of this discussion!

About our guest:

Dr. Jack West is an internationally-renowned Thoracic Oncologist. Associate Professor in the Department of Medical Oncology & Therapeutics Research at City of Hope Comprehensive Cancer Center. He is also the Clinical Executive Director of AccessHope. He completed his medical education at Harvard Medical School, and then trained at Brigham and Women’s Hospital before heading to Fred Hutchinson at the University of Washington. Twitter: @JackWestMD

References:

https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)02098-5/fulltext - IMPOWER 010 Trial

https://www.nejm.org/doi/full/10.1056/NEJMoa2027071- ADAURA Trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4032958/ - NATCH Trial

https://www.nejm.org/doi/pdf/10.1056/NEJMoa043623 - JBR.10 Trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3033998/ - Follow up to JBR.10 Trial looking at influence of EGFR status on chemotherapy response

https://www.nejm.org/doi/10.1056/NEJMoa2202170 - CHECKMATE 816

https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s - Episode 026

https://www.thefellowoncall.com/tfocpodcast/episode-001disclaimer-wfhgf-ml3b6-9m66a-8rrc4-k8w87-x7xdd-wrzye-4xg8x-t73gt-cxc5s-nmg8f-cfyd6-hgs35-5pcwx-tf6dh-trggt-xzkt7-923gg-rpjzx-6s36p-hk27n-bbpgx-jymml-9lfam-76m4s-6xae9-ws6nt-ntn8g - Episode 029

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