Preoperative (chemo)immunotherapy for stage III NSCLC

[seper]

What is the current level of evidence on the subject? Thanks

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[Palex80]

I am aware of two published trials:

SAKK 16/14:

SAKK 16/14: Durvalumab in Addition to Neoadjuvant Chemotherapy in Patients With Stage IIIA(N2) Non-Small-Cell Lung Cancer-A Multicenter Single-Arm Phase II Trial - PubMed

The addition of perioperative durvalumab to neoadjuvant chemotherapy in patients with stage IIIA(N2) non-small-cell lung cancer is safe and exceeds historical data of chemotherapy alone with a high MPR and an encouraging 1-year EFS rate of 73%.

pubmed.ncbi.nlm.nih.gov

and

NADIM:

Neoadjuvant chemotherapy and nivolumab in resectable non-small-cell lung cancer (NADIM): an open-label, multicentre, single-arm, phase 2 trial - PubMed

Bristol-Myers Squibb, Instituto de Salud Carlos III, European Union's Horizon 2020 research and innovation programme.

pubmed.ncbi.nlm.nih.gov

As far I know, these are the only two trials looking at stage III NSCLC specifically. There are other trials too, but they evaluated a wider spectrum of disease, from stage I to stage III.

 

[medgator]

Medoncs trying to take away lung from us now?

 

[Palex80]

Medoncs trying to take away lung from us now?

It may happen for resectable stage IIIA. The pCR rates are quite high with neoadjuvant IO + chemotherapy.

Adjuvant IO is also going to become s.o.c. likely within the next couple of years for patients with resected stage II-IIIA (on top or without adjuvant chemotherapy), so medoncs are likely to extrapolate that if it works in the adjuvant setting it is going to work in the neoadjuvant setting too.

 

[medgator]

It may happen for resectable stage IIIA. The pCR rates are quite high with neoadjuvant IO + chemotherapy.

Adjuvant IO is also going to become s.o.c. likely within the next couple of years for patients with resected stage II-IIIA (on top or without adjuvant chemotherapy), so medoncs are likely to extrapolate that if it works in the adjuvant setting it is going to work in the neoadjuvant setting too.

We don't typically operate on Stage III anyways (unless incidental pN2 disease found after surgery) and I wasn't keen on pre-op in those patients to begin with.

 

[RickyScott]

We don't typically operate on Stage III anyways (unless incidental pN2 disease found after surgery) and I wasn't keen on pre-op in those patients to begin with.

Our thoracic surgeon was going off on some phase 2 trial at mskcc and how he sees it opening up more stage 3 to surg. He also thinks he will be giving the io. On a separately depressing note, the company making nav bronch is trialing an attachment for ablating tumors. Our guys can already deploy sbrt fiducials in very peripheral tumors.

 

[Lamount]

With PACIFIC, it’s gonna be pretty hard for surgery to break out of single station N2… especially in the absence of pCR. Data will need to be VERY compelling.

 

[RickyScott]

With PACIFIC, it’s gonna be pretty hard for surgery to break out of single station N2… especially in the absence of pCR. Data will need to be VERY compelling.

Wasn’t IO recently approved w/postop chemo? Up until then, only chance for stage 3 pt to get IO was with pacific.

https://www.clinicaloncology.com/FDA-Watch/Article/10-21/FDA-Approves-Tecentriq-as-Adjuvant-Rx-for-Stage-II-IIIA-NSCLC/65127

 

[Palex80]

With PACIFIC, it’s gonna be pretty hard for surgery to break out of single station N2… especially in the absence of pCR. Data will need to be VERY compelling.

pCR is something med oncs love. Look at breast cancer, for instance, and how they are pushing for it there. The same goes for TNT in rectal cancer (soon without RT, likely).
Give the med oncs data on good pCR rates and they will push for that kind of treatment.

 

[radoncopotamus]

Medoncs trying to take away lung from us now?

You must not have a med onc who tries to refer N3 disease to thoracic surgery for "curative" intent in an 'academic" practice. - Sigh... Its probably just me that I have to try to stop this every time.

 

[RickyScott]

Neoadjuvant Opdivo (nivolumab) Plus Chemotherapy Significantly Improves Event-Free Survival in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate -816 Trial

CheckMate -816 is the first Phase 3 trial with an immunotherapy-based combination to demonstrate improved event-free survival and pathologic complete response in the neoadjuvant setting of non-small cell lung cancer Positive results reinforce the improved efficacy seen with Opdivo-based...

bit.ly

 

[TheWallnerus]

Neoadjuvant Opdivo (nivolumab) Plus Chemotherapy Significantly Improves Event-Free Survival in Patients with Resectable Non-Small Cell Lung Cancer in Phase 3 CheckMate -816 Trial

CheckMate -816 is the first Phase 3 trial with an immunotherapy-based combination to demonstrate improved event-free survival and pathologic complete response in the neoadjuvant setting of non-small cell lung cancer Positive results reinforce the improved efficacy seen with Opdivo-based...

bit.ly

Increased the pCR ten-fold? Whoa.

These pCR rates are not that different than the below, but I would chose the IO versus the below personally.

Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160) - PubMed

This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

pubmed.ncbi.nlm.nih.gov

 

[radiation]

pCR is something med oncs love. Look at breast cancer, for instance, and how they are pushing for it there. The same goes for TNT in rectal cancer (soon without RT, likely).
Give the med oncs data on good pCR rates and they will push for that kind of treatment.

Precision Radiotherapy: Reduction in Radiation for Oropharyngeal Cancer in the 30 ROC Trial - PubMed

Deescalation of radiotherapy to 30 Gy on the basis of intratreatment hypoxia imaging was feasible, safe, and associated with minimal toxicity. A DNA repair defect identified by WGS was predictive of response. Intratherapy personalization of chemoradiotherapy may facilitate marked deescalation of...

pubmed.ncbi.nlm.nih.gov

if only it was a drug that produced these pCRs...

a 22 pt med onc trial gets you nejm

https://www.nejm.org/doi/full/10.1056/nejmoa1716078

 

[RickyScott]

Increased the pCR ten-fold? Whoa.

These pCR rates are not that different than the below, but I would chose the IO versus the below personally.

Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160) - PubMed

This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

pubmed.ncbi.nlm.nih.gov

Absolutely. The IO is having a systemic effect as well. It also seems to work if pdl< 1%

 

[Palex80]

Increased the pCR ten-fold? Whoa.

These pCR rates are not that different than the below, but I would chose the IO versus the below personally.

Induction chemoradiation and surgical resection for superior sulcus non-small-cell lung carcinomas: long-term results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160) - PubMed

This combined-modality approach is feasible and is associated with high rates of complete resection and pathologic CR in both T3 and T4 tumors. Local control and overall survival seem markedly improved relative to previous studies of radiation plus resection.

pubmed.ncbi.nlm.nih.gov

Or any different that this one:

Effect of preoperative chemoradiation in addition to preoperative chemotherapy: a randomised trial in stage III non-small-cell lung cancer - PubMed

German Cancer Aid (Bonn, Germany).

pubmed.ncbi.nlm.nih.gov