Skilled oncologists engaged in a case-based dialogue relating to the administration of regionally superior lung most cancers on the twenty fifth Annual Worldwide Lung Most cancers Congress. The panel mentioned 2 complicated case research of a 77-year-old girl with a big smoking historical past presenting with a left hilar mass and a 73-year-old never-smoker with a cough and a lung mass.
In the course of the dialogue, oncologists answered questions on acceptable diagnostic procedures, noting the significance of thorough mediastinal staging with endobronchial ultrasound or mediastinoscopy. Optimum remedy choices, together with chemoradiation adopted by durvalumab and neoadjuvant chemoimmunotherapy adopted by surgical resection, have been additionally debated primarily based on patient-specific elements resembling resectability and desire. The optimum use of molecular testing and the combination of focused therapies into follow, significantly in oncogene-driven circumstances, was additionally mentioned.
Panelists included:
- Sarah Goldberg, MD, MPH, affiliate professor, Inside Medication, Yale Faculty of Medication; affiliate director, Medical Oncology-Hematology Program; Analysis Director, Heart for Thoracic Cancers; chief, Thoracic Oncology, Yale Most cancers Heart, New Haven, Connecticut
- Megan E. Daly, MD, professor, Medical Radiation Oncology; affiliate director, Medical Analysis; Jennifer Rene Harmon Tegley and Elizabeth Erica Harmon Endowed Chair in Most cancers Medical Analysis, College of California (UC) Davis Complete Most cancers Heart, Sacramento, California
- Percy Lee, MD, FASTRO, professor, vice chair, Medical Analysis; medical director, Orange County; medical director, Coastal Areas, Lennar Basis Most cancers Heart, Division of Radiation Oncology, Metropolis of Hope, Duarte, California
- Meghan Ramsey, MD, medical affiliate professor, the Division of Pulmonary, Allergy, and Vital Care Medication, Stanford Healthcare, Stanford, California
- Anjali Sibley MD, MPH, director, Stanford Emeryville Most cancers Heart; medical affiliate professor of medication (Oncology), Stanford College Faculty of Medication, Hematology & Medical Oncology, Stanford Healthcare, Stanford, California
- Millie Das, MD, medical affiliate professor; chief, Oncology, VA Palo Alto Well being Care System, Palo Alto, California
- Harvey I. Cross, MD, Stephen E. Banner Professor of Thoracic Oncology, Division of Cardiothoracic Surgical procedure; professor, Division of Surgical procedure, NYU Grossman Faculty of Medication, New York, New York.
Beneath is a recap of key questions, controversies, and conclusions from this panel dialogue.
Case 1
A 77-year-old girl with an 80 pack per-year smoking historical past who stop 10 years in the past presents with shortness of breath. Her chest X-ray reveals a left hilar mass, and a PET-CT scan reveals an FDG-avid 10 cm left hilar mass together with a cumbersome FDG-avid anterior mediastinal lymph node measuring 3.2 cm within the quick axis. An MRI of the mind is detrimental. A CT-guided biopsy confirms squamous non–small cell lung most cancers (NSCLC). Immunohistochemistry reveals 85% PD-L1 expression, tumor mutational burden is excessive, and next-generation sequencing identifies a PIK3CA mutation. The affected person’s ECOG efficiency standing is 1.
Query 1: Do you stage further lymph nodes within the mediastinum to find out single- vs multi-station N2 illness previous to choosing remedy choices?
Ramsey: I might agree with nearly all of the viewers [and say] that I might [perform an] endobronchial ultrasound with transbronchial needle aspiration of mediastinal lymph nodes. It will be important for staging these sufferers [to have that option]. Sure [scans] can have false negatives.
So far as transbronchial needle aspiration of mediastinal lymph nodes vs mediastinoscopy, we’re getting increasingly knowledge with this; there’s noninferiority to doing both [option] and one is way much less invasive [than the other] for the sufferers. Subsequently, it comes all the way down to the thoroughness of the process you are doing fairly than the process itself.
How thorough are you throughout transbronchial needle aspiration of mediastinal lymph nodes vs how thorough are you throughout mediastinoscopy? That is a part of what we’re doing
Query 2: What’s your normal remedy strategy? Chemoradiation adopted by consolidation durvalumab (Imfinzi), or neoadjuvant chemotherapy adopted by surgical resection?
Goldberg: As I’ve talked about, these are the sorts of circumstances we discuss throughout tumor boards, as a result of neither [option] is incorrect. They’re each cheap methods, assuming you comply with [them correctly], and it actually comes all the way down to [whether] the affected person is resectable from a surgical standpoint. That [is when] the surgeon appears on the imaging and decides if they will, as was talked about, do an R0 resection.
[Sometimes], the affected person needs to endure surgical procedure and generally folks really feel strongly [about that], which can push us by hook or by crook. [However], a few years in the past, this could have been extra easy: it will have been chemoradiation adopted by durvalumab. Now, [patients with] stage III most cancers and even cumbersome lymph nodes are nonetheless thought of [strong candidates] for surgical resection with neoadjuvant chemoimmunotherapy.
Cross: I agree with you. I feel that this can be a surgically resectable affected person. The phrase must get out not solely to medical oncologists however to surgeons [about] the [idea of the] part 3 PACIFIC [NCT02125461] trial, which actually didn’t have a surgeon evaluating these sufferers. When you have a look at the protocol and see how they staged these sufferers, there was controversy as as to whether there have been resectable sufferers, although it was nonetheless a terrific trial.
Das: The remedy radiation area is kind of giant. That is the precise affected person [to whom] we’re excited to manage neoadjuvant chemotherapy/immuno-oncology. We all know that the sufferers with stage III illness benefited most and we all know that this affected person’s PD-L1 expression degree is 85%. [They] are prone to profit and to have downstaging. I might attempt to get that affected person to go for surgical procedure if thought of a surgical candidate.
Lee: I agree with that. If it is a cumbersome major tumor within the decrease lobe, it is difficult to undergo chemoradiation in secure method. We do not know the reply right here, as there isn’t any head-to-head comparability so far as this remedy algorithm. Affected person desire is de facto, actually essential, as is a multidisciplinary strategy.
Sibley: Affected person desire is essential right here. Lots of people don’t desire radiation, and I might have chosen neoadjuvant chemotherapy per the part 3 KEYNOTE-671 trial [NCT03425643] simply because KEYNOTE-671 did embody sufferers with stage IIIB illness. That’s an possibility now with out radiation, and it did embody many sufferers with squamous illness as nicely. Plus, it provides us the chance for adjuvant remedy once we’re carried out. We noticed main pathological charges in sufferers who have been on KEYNOTE-671, so there are a variety of elements right here.
Query 3: You determine on neoadjuvant chemoimmunotherapy adopted by surgical resection for this affected person with stage IIIB NSCLC with squamous histology and a single station cumbersome anterior-posterior window N2 lymph node, PD-L1 IHC at 85%, excessive tumor mutational burden, and a PIK3CA mutation. Do you select carboplatin, paclitaxel, and nivolumab (Opdivo) adopted by surgical resection or cisplatin, gemcitabine, and pembrolizumab (Keytruda) adopted by surgical resection and adjuvant pembrolizumab?
Goldberg: I attempt to give cisplatin within the healing setting every time attainable, so when sufferers are eligible for cisplatin, I choose a cisplatin-based routine. I additionally like giving a perioperative routine as a result of then I can have the choice of giving adjuvant remedy. I wish to have the choice to doubtlessly give further immunotherapy after resection. Subsequently, I in all probability would have carried out the identical.
Das: I personally just like the carboplatin, paclitaxel, and nivolumab strategy per the part 3 CheckMate 816 trial [NCT02998528]. Te part 3 CheckMate 77T trial [NCT04025879], which additionally reveals us that we can provide out further adjuvant nivolumab afterward. There weren’t sufficient decisions for this query. It could be cheap to go along with the CheckMate 816 routine and doubtlessly proceed nivolumab as an adjuvant remedy per the CheckMate 77T trial for sufferers who do not obtain a pathologic full response, pending approval.
Case 2
A 73-year-old man with no historical past of smoking presents with a cough. A chest X-ray reveals a mass in his left decrease lobe. A PET-CT scan reveals an FDG-avid mass in the suitable decrease lobe measuring 2 cm with a typical uptake worth of 6, together with further FDG-avid hilar lymph nodes measuring 1.5 cm with a most commonplace uptake worth of 5.1, and a subcarinal lymph node measuring 1.6 cm with a most commonplace uptake worth of 6. MRI of the mind is detrimental. A CT-guided biopsy of the suitable decrease lobe confirms lung adenocarcinoma with thyroid transcription issue 1 positivity. His ECOG efficiency standing is 1.
Query 1: Do you stage the mediastinum previous to figuring out remedy choices?
Ramsey: No, we wait to substantiate the prognosis. Though this sample is kind of suspicious, we do have circumstances of [changes] that may trigger false positives. I feel it is such an important dedication. I’ll add, it isn’t unusual that we’re seeing these. I extremely encourage sufferers to get to the pulmonologist fairly than going extra of an interventional radiology route; on the identical time, it is probably the most environment friendly option to get sufferers to the docs.
Query 2: What molecular testing would you order for this affected person?
Goldberg: We do in-house testing for broad panel next-generation sequencing [NGS], in addition to PD-L1. We do not have speedy EGFR testing, though we’ll be getting it very quickly.
Right here, an important factor is broad genomic profiling. You possibly can even query the worth of PD-L1 on this affected person who’s a never-smoker. PCR can also be useful. Selections are wanted on these sufferers shortly and [it can take] a few weeks for NGS [results] to come back again. Although speedy testing in these small panels the place we’re simply getting 1 or 2 genes has fallen out of favor, in some circumstances [it can be helpful].
Sibley: Many people within the viewers work in group facilities. It is crucial to make sure that we do have this out there and, if not, work out a option to work with pathology and guarantee that there’s good communication to check for this stuff as nicely, as we simply talked about, immunotherapy regimens. We have to be sure that now we have a group in place in every single place that may present and help multidisciplinary care.
That goes again to the relationships between suppliers and oncologists, in addition to between suppliers and group hospitals. In fact, genomic profiling is a necessity, however we’d like to ensure everyone can do that.
Goldberg: For some time, EGFR [mutations were] essential on this setting, however now ALK mutations are additionally essential. These are the two [targets] that now we have probably the most knowledge for… however it’s possible you’ll need to take into consideration focused therapies for sufferers with ROS1 or RET mutations, fully extrapolating from different research.
It is useful to get the broad take a look at it is only a matter of timing and if you’re pressed to get testing outcomes again. In a great world [you do all], however in any other case, a broader panel the place you are getting all of all of your actionable alterations, is essential on this setting.
We’re undoubtedly in want of extra novel assays, whether or not or not it’s blood or in any other case, so we will get these outcomes shortly and never must get these massive biopsies.
Query 3: What normal remedy strategy would you make the most of for this never-smoking 73-year-old affected person with stage IIIA, NSCLC-adenocarcinoma?
Lee: The selection of chemoradiation adopted by osimertinib [Tagrisso] is a really cheap alternative. Now, now we have 2 good choices for sufferers. Chemoradiation adopted by osimertinib, appears excellent and promising; nevertheless, we need to see the long-term outcomes so far as survival. The indefinite use of osimertinib troubles some folks, [from] oncologists and physicians [to] sufferers. What we’ll see is different subsets that do not want them for the whole period of their life. Nonetheless, once more, it is affected person alternative.
Ramsey: The query right here is, you realize, clearly for a surgeon to determine whether or not the affected person remains to be thought of resectable and if they’re, I feel that the strategy of neoadjuvant chemotherapy adopted by surgical procedure adopted by adjuvant osimertinib is affordable. These are the circumstances [we bring to the] tumor board. General, chemoradiation adopted by osimertinib [for life] is a really cheap possibility as a result of we all know that these sufferers are at excessive threat of recurrence and development…Both of these choices is ok, though something with immunotherapy needs to be out.
Query 5: Amongst sufferers with oncogene pushed mutations, which genotypes and coverings would you take into account for sufferers with unresectable stage III illness after completion of chemoradiation?
Goldberg: The info for osimertinib within the EGFR-mutated setting is so robust. We see how terribly these sufferers do with chemoradiation alone. It is tempting to manage it past these with EGFR mutations, though we do not have knowledge [to support this]. Extrapolating [data] from the part 3 LAURA [NCT03521154] and ALINA [NCT03456076] trials, I might in all probability give alectinib [Alecensa] to sufferers with ALK-positive lung most cancers after chemoradiation, regardless of the shortage of information. I’d talk about it with sufferers; I feel it is one thing to think about. Nonetheless, I do not know that we will get many trials of all these subsets, so I feel this extrapolation goes to be occurring for a very long time.
Reference
Case-Based mostly Panel Dialogue: Regionally Superior Illness. Introduced at: twenty fifth Annual Worldwide Lung Most cancers Congress; July 25-27, 2024; Huntington Seashore, CA.
