Not always; it depends on the type of lung cancer, its stage and genetic tests on the tumour [1]. In non-small cell lung cancer, chemotherapy combined with surgery increases the chance of survival in stages 2 and 3, today often together with immunotherapy and before surgery, but it brings no benefit in small stage 1 tumours [2, 5, 7]. If the tumour has an EGFR mutation or an ALK change, a targeted tablet plays the main role [11, 13], and in advanced disease with high PD-L1, immunotherapy alone can take the place of chemotherapy [16]; but in small cell lung cancer, chemotherapy is still the foundation of treatment [20].
Key points
- First, the type of lung cancer must be clear: non-small cell lung cancer (the more common type) and small cell lung cancer are treated differently [1, 20].
- Small stage 1 tumours: chemotherapy after surgery has not shown a benefit in them [2].
- Stages 2 and 3: chemotherapy, today often together with immunotherapy and before surgery, has kept more patients alive [2, 5, 7].
- EGFR mutation or ALK change: after surgery, osimertinib tablets (after chemotherapy or without it) and alectinib tablets (instead of chemotherapy) have greatly lowered the risk of the cancer coming back [11, 13].
- Advanced disease with high PD-L1: immunotherapy alone worked better than chemotherapy and caused fewer serious side effects [15, 16].
- Small cell cancer: chemotherapy is part of all its standard treatments [20].
First: which type of lung cancer, and which tests?
There are two main types of lung cancer: non-small cell, which is more common, and small cell; they are treated differently [1, 20]. In non-small cell lung cancer, a few tests on a tumour sample also change the decision [1]:
- EGFR mutation and ALK change: if one of these is present, targeted tablets made for them are used, even after surgery [12, 14].
- PD-L1: the amount of this protein in the tumour shows how likely immunotherapy is to help, and whether in advanced disease it can be given without chemotherapy [15].
So before treatment starts, ask your doctor whether these tests have been done. Read more: Chemotherapy or targeted therapy? Ask this before treatment starts.
Early stage: is chemotherapy needed after surgery?
When non-small cell lung cancer is removed by surgery, chemotherapy after the operation aims to destroy any cancer cells left behind; it is usually 4 three-week cycles with a platinum drug such as cisplatin [2, 13]. Its benefit depends on the stage: in a review of 5 large studies with more than 4,500 patients, chemotherapy increased the chance of survival in stages 2 and 3, but brought no benefit in small stage 1 tumours and may even have done harm. Overall, about 5 more patients in every 100 were alive after 5 years [2].
| Situation | Usually | What has been shown |
|---|---|---|
| Small stage 1 (1A) | Chemotherapy is not recommended; regular follow-up | Chemotherapy showed no benefit [2] |
| Stage 1B | An individual decision with your doctor | A small, unproven benefit [2] |
| Operable stage 2 and 3, without an EGFR or ALK change | Chemotherapy with immunotherapy, often before surgery; or chemotherapy after surgery followed by immunotherapy | More patients stayed alive or their disease came back later [2, 5, 7, 24] |
| With an EGFR mutation | Osimertinib tablets for up to 3 years after surgery, after chemotherapy or without it | The risk of death was almost halved [11, 12] |
| With an ALK change | Alectinib tablets for 2 years instead of chemotherapy | The cancer came back much less often than with chemotherapy [13] |
Immunotherapy with chemotherapy before surgery, and alectinib after surgery, are used for tumours of 4 cm or larger or with lymph node involvement [8, 9, 14]. A multidisciplinary team makes the final decision.
For physicians
LACE (5 trials, 4,584 resected patients; cisplatin-based chemotherapy): HR for death 0.89 (95% CI 0.82 to 0.96; P=0.005) and a 5-year absolute benefit of 5.4%; the benefit varied with stage (P for trend=0.04): IA HR 1.40 (0.95 to 2.06), IB 0.93 (0.78 to 1.10), II 0.83 (0.73 to 0.95) and III 0.83 (0.72 to 0.94); with vinorelbine HR 0.80; the effect was greater with better performance status and did not interact with age, sex or histology [2]. 2010 meta-analysis (34 comparisons, 8,447 patients): HR 0.86 and 5-year survival from 60% to 64% [3].
Adjuvant immunotherapy after chemotherapy: PEARLS/KEYNOTE-091 (IB with tumours ≥4 cm to IIIA, regardless of PD-L1; pembrolizumab for up to 18 cycles): median DFS 53.6 vs 42.0 months (HR 0.76) [24]; IMpower010 (atezolizumab for one year after 1 to 4 cycles of platinum-based chemotherapy): DFS HR 0.66 in II–IIIA with PD-L1 ≥1% and 0.79 in all II–IIIA [25]. FDA label for pembrolizumab: single-agent adjuvant treatment after resection and platinum-based chemotherapy in stage IB (T2a ≥4 cm), II or IIIA [9].
Treatment before surgery: chemotherapy with immunotherapy
For tumours of 4 cm or larger, or when lymph nodes are involved, a few cycles of chemotherapy with immunotherapy (nivolumab or pembrolizumab) are now often given before surgery [8, 9]. Chemotherapy is still needed in this approach: immunotherapy is added to it rather than replacing it [4, 6].
In a large study, with 3 cycles of nivolumab plus chemotherapy before surgery, no cancer was left at the time of surgery in about 1 in 4 patients, which was seen much less often with chemotherapy alone [4]; after 5 years, more patients were also alive [5]. In another study in which pembrolizumab was given before and after surgery, the number of patients without the cancer coming back after 5 years almost doubled, and more patients stayed alive [7].
For physicians
CheckMate 816 (IB to IIIA; 3 cycles of nivolumab plus platinum-based chemotherapy vs chemotherapy alone): median EFS 31.6 vs 20.8 months (HR 0.63; 97.38% CI 0.43 to 0.91); pCR 24.0% vs 2.2%; surgery in 83.2% vs 75.4%; grade 3 or 4 treatment-related adverse events 33.5% vs 36.9% [4]. Final OS analysis (median follow-up 68.4 months): HR 0.72 (95% CI 0.523 to 0.998; P=0.048) and 5-year OS 65.4% vs 55.0%; in the nivolumab group, 5-year OS 95.3% with pCR and 55.7% without pCR (exploratory analysis) [5].
KEYNOTE-671 (II, IIIA or IIIB (N2); 4 cycles of pembrolizumab 200 mg with cisplatin-based chemotherapy, surgery, then up to 13 cycles of pembrolizumab): 24-month EFS 62.4% vs 40.6% (HR 0.58); pCR 18.1% vs 4.0%; grade 3 or higher treatment-related adverse events 44.9% vs 37.3% [6]. 5-year follow-up: EFS 49.9% vs 26.5% (HR 0.58) and OS 64.6% vs 53.6% (HR 0.74) [7]. FDA labels: nivolumab 360 mg with platinum-doublet chemotherapy on the same day, every 3 weeks for 3 cycles (neoadjuvant, tumours ≥4 cm or N-positive); the perioperative nivolumab regimen only with no known EGFR mutation or ALK rearrangement [8]. Pembrolizumab in resectable NSCLC 200 mg every 3 weeks or 400 mg every 6 weeks, with platinum-containing chemotherapy before surgery and then as a single agent afterwards [9].
EGFR or ALK: a targeted tablet instead of chemotherapy, or after it
EGFR mutation: after surgery, and after chemotherapy if your doctor thinks it is needed, osimertinib tablets are taken once a day for up to 3 years [10, 12]. In a large study, this tablet almost halved the risk of death [11]. Most patients in this study had also received chemotherapy before the tablet; in other words, the tablet was not tested as a replacement for chemotherapy [12].
ALK change: in these patients, alectinib tablets for 2 years were compared directly with chemotherapy and lowered the risk of the cancer coming back or death by about three-quarters; so here the tablet takes the place of chemotherapy [13].
Advanced disease: if the cancer has spread and the tumour has an EGFR mutation, a targeted tablet is the foundation of treatment; sometimes chemotherapy is given with the tablet, which helped patients live longer but also caused more serious side effects [18, 19]. Read more: Treating EGFR-mutated lung cancer: a tablet instead of chemotherapy.
For physicians
ADAURA (682 patients with stage IB to IIIA and exon 19 deletion or L858R; osimertinib 80 mg daily or placebo for up to 3 years): 24-month DFS in II–IIIA 90% vs 44% (HR 0.17) and in the overall population 89% vs 52% (HR 0.20) [10]; 5-year OS in II–IIIA 85% vs 73% (HR 0.49; 95.03% CI 0.33 to 0.73) and in the overall population 88% vs 78% (HR 0.49) [11]. 60% of patients had received adjuvant chemotherapy before randomisation (27% in IB, 70% in II and 79% in IIIA) [12].
ALINA (257 ALK-positive patients, IB with tumours ≥4 cm to IIIA per AJCC 7th edition; alectinib 600 mg twice daily for 24 months vs four 21-day cycles of platinum-based chemotherapy): 2-year DFS in II–IIIA 93.8% vs 63.0% (HR 0.24) and in the ITT population 93.6% vs 63.7% (HR 0.24); CNS disease-free survival HR 0.22; OS data were still immature [13]. FDA label: adjuvant alectinib after resection of ALK-positive NSCLC (tumours ≥4 cm or N-positive) [14].
Advanced EGFR-positive disease: FLAURA, median OS 38.6 months with osimertinib vs 31.8 months with gefitinib or erlotinib (HR 0.80) [18]; FLAURA2, osimertinib plus pemetrexed–platinum vs osimertinib alone: median OS 47.5 vs 37.6 months (HR 0.77), with grade 3 or higher adverse events in 70% vs 34% [19]. Regimens: Adjuvant alectinib (ALINA) · Osimertinib with pemetrexed and platinum (FLAURA2).
Advanced disease: is immunotherapy alone enough?
If non-small cell lung cancer has spread and the tumour has no EGFR mutation or ALK change, the amount of PD-L1 matters. When at least half of the tumour cells have PD-L1, immunotherapy with pembrolizumab alone worked better than chemotherapy: the disease progressed later and serious side effects were fewer [15], and after 5 years almost twice as many patients were alive [16]. So in this group chemotherapy can be left out; although, depending on your situation, your doctor may give immunotherapy together with chemotherapy [16, 17].
When PD-L1 is lower, immunotherapy is usually given with chemotherapy; in a large study, this combination helped patients live longer than chemotherapy alone, whatever the amount of PD-L1 [17]. Read more: What is cancer immunotherapy?
For physicians
KEYNOTE-024 (305 untreated patients, TPS ≥50%, no EGFR/ALK; pembrolizumab 200 mg every 3 weeks vs platinum-based chemotherapy, with crossover allowed): median PFS 10.3 vs 6.0 months (HR 0.50); HR for death 0.60; response 44.8% vs 27.8%; grade 3 to 5 treatment-related adverse events 26.6% vs 53.3% [15]. 5-year follow-up (effective crossover 66.0%): median OS 26.3 vs 13.4 months (HR 0.62) and 5-year OS 31.9% vs 16.3% [16]. KEYNOTE-189 (non-squamous, no EGFR/ALK; pembrolizumab plus pemetrexed–platinum): OS HR 0.60 and 5-year OS 19.4% vs 11.3%, regardless of PD-L1 [17]. Regimens: Pembrolizumab alone (KEYNOTE-024) · Carboplatin, pemetrexed and pembrolizumab · Carboplatin, paclitaxel and pembrolizumab.
Small cell lung cancer: chemotherapy is still the foundation of treatment
Most people with small cell lung cancer already have disease that has spread when it is diagnosed [22], and chemotherapy is part of almost all standard treatments for this cancer [20]:
- Limited stage: chemotherapy with radiotherapy to the chest, followed in some patients by immunotherapy; even when the tumour is removed by surgery, chemotherapy is given afterwards [20].
- Extensive (spread) stage: chemotherapy with immunotherapy (atezolizumab or durvalumab) [20]; adding immunotherapy to chemotherapy helped patients live longer [21, 22].
Read more: Small cell lung cancer: how it differs and how it is treated
For physicians
IMpower133 (403 patients with untreated ES-SCLC; carboplatin–etoposide with atezolizumab or placebo for four 21-day cycles, then maintenance): median OS 12.3 vs 10.3 months (HR 0.70) and median PFS 5.2 vs 4.3 months (HR 0.77) [21]. CASPIAN (durvalumab with platinum–etoposide for up to 4 cycles, then maintenance): median OS 13.0 vs 10.3 months (HR 0.73) [22]. ADRIATIC (LS-SCLC without progression after concurrent platinum-based chemoradiotherapy; durvalumab 1500 mg every 4 weeks for up to 24 months): median OS 55.9 vs 33.4 months (HR 0.73) and median PFS 16.6 vs 9.2 months (HR 0.76) [23]. Regimen: Carboplatin–etoposide with atezolizumab or durvalumab.
Older age and physical fitness
Age alone is not a reason to leave out chemotherapy. In a large review of studies of chemotherapy after surgery, the effect of chemotherapy did not change with age, but it was greater in patients who were physically fitter [2]. In people aged 70 to 89 with advanced cancer, two-drug chemotherapy with carboplatin helped them live longer than a single drug, although it caused more side effects [26]. Your doctor weighs up your fitness, other illnesses and your wishes together.
For physicians
IFCT-0501 (before the immunotherapy era; 451 patients aged 70 to 89 with PS 0 to 2; carboplatin on day 1 plus paclitaxel on days 1, 8 and 15 in 4-week cycles, vs vinorelbine or gemcitabine alone): median OS 10.3 vs 6.2 months (HR 0.64); 1-year survival 44.5% vs 25.4%; decreased neutrophil count 48.4% vs 12.4% [26]. Tools: Geriatric assessment before chemotherapy · CARG score · ECOG and Karnofsky.
When is it safe to go without chemotherapy, and when is it not?
Usually no chemotherapy
- A small stage 1 tumour after surgery [2]
- An ALK change after surgery: alectinib tablets instead of chemotherapy [13]
- Advanced disease with high PD-L1 and no EGFR or ALK change: immunotherapy alone is an option [15, 16]
- Advanced disease with an EGFR mutation: a targeted tablet is the foundation of treatment, with or without chemotherapy [18, 19]
Leaving it out is dangerous
- Operable stage 2 and 3 without an EGFR or ALK change: chemotherapy, often with immunotherapy, increases the chance of survival [2, 5, 7]
- Small cell lung cancer: chemotherapy is the foundation of treatment [20, 21]
- Advanced disease with low PD-L1: chemotherapy with immunotherapy helped patients live longer [17]
Do not drop or put off the recommended treatment on your own. If you are worried about side effects, ask what other options there are and how much each option would help you. If genetic tests on the tumour or a PD-L1 test have not yet been done, ask whether they are needed before treatment starts.
Questions to ask your doctor
- "Is my cancer non-small cell or small cell? What is its stage?"
- "Have EGFR, ALK and PD-L1 tests been done on my tumour, and what were the results?"
- "What is the aim of my treatment: cure or control of the disease?"
- "Will immunotherapy or a targeted tablet replace chemotherapy for me, or be given with it?"
- "Will I have chemotherapy before or after surgery? How many cycles?"
- "How much will this treatment help me, and what side effects does it have?"
To prepare, read: What is chemotherapy and how is it given?, Is lung cancer curable? and Lung cancer.
Frequently asked questions
Is chemotherapy needed for stage 1 lung cancer?
Does immunotherapy replace chemotherapy?
Does a targeted tablet replace chemotherapy?
It depends on the genetic change. After surgery, with an ALK change, alectinib tablets worked better than chemotherapy [13]; with an EGFR mutation, osimertinib tablets are given after chemotherapy (if it is needed) [12]. In advanced disease with an EGFR mutation, a targeted tablet is the foundation of treatment [18, 19].
How many chemotherapy sessions are there for lung cancer?
After surgery, usually 4 three-week cycles [13]. Before surgery, together with immunotherapy, 3 cycles with nivolumab or 4 cycles with pembrolizumab [5, 6]. See How many chemotherapy sessions will I need?
Can older people have chemotherapy?
What happens if I do not have chemotherapy?
It depends on the type and stage of the cancer. In operable stage 2 and 3 disease, chemotherapy, especially together with immunotherapy, has kept more patients alive [2, 5, 7]; in small cell cancer, too, chemotherapy is the foundation of treatment [20]. Ask your doctor what other options there are in your situation.
Scientific evidence
Key studies in the evidence library
10 itemsOverall Survival with Neoadjuvant Nivolumab plus Chemotherapy in Lung Cancer
Neoadjuvant pembrolizumab plus chemotherapy followed by adjuvant pembrolizumab compared with neoadjuvant chemotherapy alone in patients with early-stage non-small-cell lung cancer (KEYNOTE-671): a randomised, double-blind, placebo-controlled, phase 3 trial
Five-Year Outcomes of Perioperative Pembrolizumab for Early-Stage Non-Small-Cell Lung Cancer From the Randomized KEYNOTE-671 Study
Overall Survival with Osimertinib in Resected EGFR-Mutated NSCLC
Pembrolizumab versus Chemotherapy for PD-L1–Positive Non–Small-Cell Lung Cancer
Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC
Alectinib in Resected ALK-Positive Non–Small-Cell Lung Cancer
First-Line Atezolizumab plus Chemotherapy in Extensive-Stage Small-Cell Lung Cancer
Durvalumab plus platinum–etoposide versus platinum–etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial
Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer
Related links
Related cancer types
Related questions
References
26 referencesShow all references, 12 with a study cardClose the reference list
Numbers in the text, such as [1], refer to these sources. Sources with a “Study card” button are summarised in the site’s evidence library.
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- 3Adjuvant chemotherapy, with or without postoperative radiotherapy, in operable non-small-cell lung cancer: two meta-analyses of individual patient data
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- 23Durvalumab after Chemoradiotherapy in Limited-Stage Small-Cell Lung Cancer
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- 25Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial
- 26
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